Genetic Variant SEMA3A:c.1494+132A>C (chr7-83985304-T-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_006080.3(SEMA3A):c.1494+132A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 630,146 control chromosomes in the GnomAD database, including 49,472 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.38 ( 11626 hom., cov: 32)

Exomes 𝑓: 0.38 ( 37846 hom. )

Consequence

SEMA3A
NM_006080.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.115

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 7-83985304-T-G is Benign according to our data. Variant chr7-83985304-T-G is described in ClinVar as [Benign]. Clinvar id is 1245431.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SEMA3A	NM_006080.3 link	c.1494+132A>C	intron_variant	Intron 13 of 16	ENST00000265362.9	NP_006071.1	Q14563
SEMA3A	XM_005250110.4 link	c.1494+132A>C	intron_variant	Intron 16 of 19		XP_005250167.1	Q14563
SEMA3A	XM_047419751.1 link	c.1494+132A>C	intron_variant	Intron 17 of 20		XP_047275707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3A	ENST00000265362.9 link	c.1494+132A>C		intron_variant	Intron 13 of 16	1	NM_006080.3	ENSP00000265362.3		Q14563
SEMA3A	ENST00000436949.5 link	c.1494+132A>C		intron_variant	Intron 14 of 17	5		ENSP00000415260.1		Q14563

Frequencies

GnomAD3 genomes

AF:

0.382

AC:

58023

AN:

151856

Hom.:

11629

Cov.:

show subpopulations

Gnomad AFR

AF:

0.354

Gnomad AMI

AF:

0.553

Gnomad AMR

AF:

0.322

Gnomad ASJ

AF:

0.375

Gnomad EAS

AF:

0.0589

Gnomad SAS

AF:

0.240

Gnomad FIN

AF:

0.421

Gnomad MID

AF:

0.478

Gnomad NFE

AF:

0.438

Gnomad OTH

AF:

0.408

GnomAD4 exome

AF:

0.381

AC:

182223

AN:

478174

Hom.:

37846

AF XY:

0.378

AC XY:

96213

AN XY:

254776

show subpopulations

Gnomad4 AFR exome

AF:

0.356

Gnomad4 AMR exome

AF:

0.239

Gnomad4 ASJ exome

AF:

0.370

Gnomad4 EAS exome

AF:

0.0526

Gnomad4 SAS exome

AF:

0.247

Gnomad4 FIN exome

AF:

0.419

Gnomad4 NFE exome

AF:

0.436

Gnomad4 OTH exome

AF:

0.385

GnomAD4 genome

AF:

0.382

AC:

58041

AN:

151972

Hom.:

11626

Cov.:

AF XY:

0.375

AC XY:

27855

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.354

Gnomad4 AMR

AF:

0.322

Gnomad4 ASJ

AF:

0.375

Gnomad4 EAS

AF:

0.0590

Gnomad4 SAS

AF:

0.240

Gnomad4 FIN

AF:

0.421

Gnomad4 NFE

AF:

0.438

Gnomad4 OTH

AF:

0.406

Alfa

AF:

0.265

Hom.:

680

Bravo

AF:

0.374

Asia WGS

AF:

0.172

AC:

599

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 09, 2018

GeneDx

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

-0.85

CADD

Benign

1.8

DANN

Benign

0.64

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