1-156177535-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_022367.4(SEMA4A):c.*538T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 182,336 control chromosomes in the GnomAD database, including 11,750 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 9905 hom., cov: 31)

Exomes 𝑓: 0.32 ( 1845 hom. )

Consequence

SEMA4A
NM_022367.4 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.51

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 1-156177535-T-C is Benign according to our data. Variant chr1-156177535-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 292867.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA4A	NM_022367.4 link	c.*538T>C		3_prime_UTR_variant	Exon 15 of 15	ENST00000368285.8	NP_071762.2	Q9H3S1-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SEMA4A	ENST00000368285.8 link	c.*538T>C	3_prime_UTR_variant	Exon 15 of 15	1	NM_022367.4	ENSP00000357268.3	Q9H3S1-1
SEMA4A	ENST00000355014.6 link	c.*538T>C	3_prime_UTR_variant	Exon 15 of 15	1		ENSP00000347117.2	Q9H3S1-1
SEMA4A	ENST00000368282.1 link	c.*538T>C	3_prime_UTR_variant	Exon 14 of 14	1		ENSP00000357265.1	Q9H3S1-1
SEMA4A	ENST00000368284.5 link	c.*538T>C	3_prime_UTR_variant	Exon 13 of 13	2		ENSP00000357267.1	Q9H3S1-2

Frequencies

GnomAD3 genomes

AF:

0.353

AC:

53593

AN:

151824

Hom.:

9892

Cov.:

show subpopulations

Gnomad AFR

AF:

0.337

Gnomad AMI

AF:

0.311

Gnomad AMR

AF:

0.316

Gnomad ASJ

AF:

0.391

Gnomad EAS

AF:

0.0238

Gnomad SAS

AF:

0.243

Gnomad FIN

AF:

0.402

Gnomad MID

AF:

0.318

Gnomad NFE

AF:

0.395

Gnomad OTH

AF:

0.353

GnomAD4 exome

AF:

0.321

AC:

9763

AN:

30392

Hom.:

1845

Cov.:

AF XY:

0.321

AC XY:

5053

AN XY:

15764

show subpopulations

Gnomad4 AFR exome

AF:

0.344

Gnomad4 AMR exome

AF:

0.279

Gnomad4 ASJ exome

AF:

0.365

Gnomad4 EAS exome

AF:

0.0353

Gnomad4 SAS exome

AF:

0.265

Gnomad4 FIN exome

AF:

0.380

Gnomad4 NFE exome

AF:

0.373

Gnomad4 OTH exome

AF:

0.367

GnomAD4 genome

AF:

0.353

AC:

53635

AN:

151944

Hom.:

9905

Cov.:

AF XY:

0.349

AC XY:

25934

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.337

Gnomad4 AMR

AF:

0.315

Gnomad4 ASJ

AF:

0.391

Gnomad4 EAS

AF:

0.0239

Gnomad4 SAS

AF:

0.243

Gnomad4 FIN

AF:

0.402

Gnomad4 NFE

AF:

0.395

Gnomad4 OTH

AF:

0.350

Alfa

AF:

0.381

Hom.:

16145

Bravo

AF:

0.344

Asia WGS

AF:

0.144

AC:

500

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Retinitis Pigmentosa, Recessive

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Cone-rod dystrophy 10

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Retinitis pigmentosa

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: 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

-0.81

CADD

Benign

DANN

Benign

0.71

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over