Genetic Variant ENST00000448879.5:c.-168-31582G>A (chr7-84338874-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000448879.5(SEMA3A):c.-168-31582G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0146 in 152,148 control chromosomes in the GnomAD database, including 96 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.015 ( 96 hom., cov: 32)

Consequence

SEMA3A
ENST00000448879.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.223

Publications

0 publications found

Variant links:

Genes affected

SEMA3A (HGNC:10723): (semaphorin 3A) This gene is a member of the semaphorin family and encodes a protein with an Ig-like C2-type (immunoglobulin-like) domain, a PSI domain and a Sema domain. This secreted protein can function as either a chemorepulsive agent, inhibiting axonal outgrowth, or as a chemoattractive agent, stimulating the growth of apical dendrites. In both cases, the protein is vital for normal neuronal pattern development. Increased expression of this protein is associated with schizophrenia and is seen in a variety of human tumor cell lines. Also, aberrant release of this protein is associated with the progression of Alzheimer's disease. [provided by RefSeq, Jul 2008]

SEMA3A Gene-Disease associations (from GenCC):

skeletal dysplasia
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
hypogonadotropic hypogonadism 16 with or without anosmia
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
multiple congenital anomalies/dysmorphic syndrome
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
Brugada syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Kallmann syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SEMA3A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3A	XM_005250110.4 link	c.-168-31582G>A		intron_variant	Intron 2 of 19		XP_005250167.1	Q14563
SEMA3A	XM_047419751.1 link	c.-258-31582G>A		intron_variant	Intron 2 of 20		XP_047275707.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
SEMA3A	ENST00000448879.5 link	c.-168-31582G>A	intron_variant	Intron 3 of 4	5	ENSP00000402093.1	A0A0C4DG50
SEMA3A	ENST00000424555.5 link	c.-168-31582G>A	intron_variant	Intron 2 of 3	4	ENSP00000404800.1	C9JD25
SEMA3A	ENST00000471474.5 link	n.373-31582G>A	intron_variant	Intron 2 of 3	5
SEMA3A	ENST00000490883.1 link	n.152-31582G>A	intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.0146

AC:

2218

AN:

152030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00227

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0520

Gnomad ASJ

AF:

0.0207

Gnomad EAS

AF:

0.153

Gnomad SAS

AF:

0.0104

Gnomad FIN

AF:

0.0103

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00391

Gnomad OTH

AF:

0.0187

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0146

AC:

2214

AN:

152148

Hom.:

Cov.:

AF XY:

0.0163

AC XY:

1209

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.00226

AC:

AN:

41522

American (AMR)

AF:

0.0518

AC:

791

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.0207

AC:

AN:

3470

East Asian (EAS)

AF:

0.153

AC:

792

AN:

5164

South Asian (SAS)

AF:

0.0102

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0103

AC:

109

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00391

AC:

266

AN:

67982

Other (OTH)

AF:

0.0180

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

108

216

325

433

541

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0112

Hom.:

Bravo

AF:

0.0189

Asia WGS

AF:

0.0690

AC:

241

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

4.9

(source)

DANN

Benign

0.58

PhyloP100

0.22

Splicing

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

Computational scores

Splicing

Publications

Other links and lift over