NM_022367.4:c.1434+20T>G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_022367.4(SEMA4A):c.1434+20T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

SEMA4A
NM_022367.4 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.461

Publications

0 publications found

Variant links:

Genes affected

SEMA4A (HGNC:10729): (semaphorin 4A) This gene encodes a member of the semaphorin family of soluble and transmembrane proteins. Semaphorins are involved in numerous functions, including axon guidance, morphogenesis, carcinogenesis, and immunomodulation. The encoded protein is a single-pass type I membrane protein containing an immunoglobulin-like C2-type domain, a PSI domain and a sema domain. It inhibits axonal extension by providing local signals to specify territories inaccessible for growing axons. It is an activator of T-cell-mediated immunity and suppresses vascular endothelial growth factor (VEGF)-mediated endothelial cell migration and proliferation in vitro and angiogenesis in vivo. Mutations in this gene are associated with retinal degenerative diseases including retinitis pigmentosa type 35 (RP35) and cone-rod dystrophy type 10 (CORD10). Multiple alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, Sep 2010]

SEMA4A Gene-Disease associations (from GenCC):

cone-rod dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
familial colorectal cancer type X
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
retinitis pigmentosa 35
Inheritance: AR, Unknown Classification: LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
cone-rod dystrophy 10
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
Lynch syndrome
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

SEMA4A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 1-156174960-T-G is Benign according to our data. Variant chr1-156174960-T-G is described in CliVar as Likely_benign. Clinvar id is 261575.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-156174960-T-G is described in CliVar as Likely_benign. Clinvar id is 261575.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-156174960-T-G is described in CliVar as Likely_benign. Clinvar id is 261575.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-156174960-T-G is described in CliVar as Likely_benign. Clinvar id is 261575.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-156174960-T-G is described in CliVar as Likely_benign. Clinvar id is 261575.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-156174960-T-G is described in CliVar as Likely_benign. Clinvar id is 261575.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-156174960-T-G is described in CliVar as Likely_benign. Clinvar id is 261575.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-156174960-T-G is described in CliVar as Likely_benign. Clinvar id is 261575.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-156174960-T-G is described in CliVar as Likely_benign. Clinvar id is 261575.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-156174960-T-G is described in CliVar as Likely_benign. Clinvar id is 261575.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-156174960-T-G is described in CliVar as Likely_benign. Clinvar id is 261575.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-156174960-T-G is described in CliVar as Likely_benign. Clinvar id is 261575.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-156174960-T-G is described in CliVar as Likely_benign. Clinvar id is 261575.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-156174960-T-G is described in CliVar as Likely_benign. Clinvar id is 261575.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-156174960-T-G is described in CliVar as Likely_benign. Clinvar id is 261575.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-156174960-T-G is described in CliVar as Likely_benign. Clinvar id is 261575.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-156174960-T-G is described in CliVar as Likely_benign. Clinvar id is 261575.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-156174960-T-G is described in CliVar as Likely_benign. Clinvar id is 261575.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-156174960-T-G is described in CliVar as Likely_benign. Clinvar id is 261575.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-156174960-T-G is described in CliVar as Likely_benign. Clinvar id is 261575.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-156174960-T-G is described in CliVar as Likely_benign. Clinvar id is 261575.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-156174960-T-G is described in CliVar as Likely_benign. Clinvar id is 261575.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-156174960-T-G is described in CliVar as Likely_benign. Clinvar id is 261575.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-156174960-T-G is described in CliVar as Likely_benign. Clinvar id is 261575.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-156174960-T-G is described in CliVar as Likely_benign. Clinvar id is 261575.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-156174960-T-G is described in CliVar as Likely_benign. Clinvar id is 261575.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-156174960-T-G is described in CliVar as Likely_benign. Clinvar id is 261575.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA4A	NM_022367.4 link	c.1434+20T>G		intron_variant	Intron 12 of 14	ENST00000368285.8	NP_071762.2	Q9H3S1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA4A	ENST00000368285.8 link	c.1434+20T>G		intron_variant	Intron 12 of 14	1	NM_022367.4	ENSP00000357268.3		Q9H3S1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000795

AC:

AN:

251482

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000450

AC:

AN:

1112012

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.4

(source)

DANN

Benign

0.37

PhyloP100

-0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over