chr7-83961536-T-C

Position:

• chr7-83961536-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_006080.3(SEMA3A):​c.2151A>G​(p.Thr717=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.619 in 1,613,714 control chromosomes in the GnomAD database, including 311,094 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.59 (26405 hom., cov: 32)
  • Exomes 𝑓: 0.62 (284689 hom.)
• Consequence: SEMA3A NM_006080.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.09

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 7-83961536-T-C is Benign according to our data. Variant chr7-83961536-T-C is described in ClinVar as [Benign]. Clinvar id is 194754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-83961536-T-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-1.09 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA3A	NM_006080.3	c.2151A>G	p.Thr717=	synonymous_variant	17/17	ENST00000265362.9
SEMA3A	XM_005250110.4	c.2151A>G	p.Thr717=	synonymous_variant	20/20
SEMA3A	XM_047419751.1	c.2151A>G	p.Thr717=	synonymous_variant	21/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA3A	ENST00000265362.9	c.2151A>G	p.Thr717=	synonymous_variant	17/17	1	NM_006080.3	P1
SEMA3A	ENST00000436949.5	c.2151A>G	p.Thr717=	synonymous_variant	18/18	5		P1

Frequencies

GnomAD3 genomes AF: 0.585 AC: 88891 AN: 151880 Hom.: 26389 Cov.: 32

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.692

Gnomad SAS AF: 0.597

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.627

Gnomad OTH AF: 0.626

GnomAD3 exomes AF: 0.616 AC: 154900 AN: 251352 Hom.: 48201 AF XY: 0.616 AC XY: 83701 AN XY: 135848

Gnomad AFR exome AF: 0.490

Gnomad AMR exome AF: 0.656

Gnomad ASJ exome AF: 0.632

Gnomad EAS exome AF: 0.707

Gnomad SAS exome AF: 0.589

Gnomad FIN exome AF: 0.548

Gnomad NFE exome AF: 0.626

Gnomad OTH exome AF: 0.619

GnomAD4 exome AF: 0.623 AC: 910368 AN: 1461718 Hom.: 284689 Cov.: 63 AF XY: 0.623 AC XY: 452812 AN XY: 727186

Gnomad4 AFR exome AF: 0.491

Gnomad4 AMR exome AF: 0.656

Gnomad4 ASJ exome AF: 0.629

Gnomad4 EAS exome AF: 0.668

Gnomad4 SAS exome AF: 0.592

Gnomad4 FIN exome AF: 0.549

Gnomad4 NFE exome AF: 0.630

Gnomad4 OTH exome AF: 0.615

GnomAD4 genome AF: 0.585 AC: 88939 AN: 151996 Hom.: 26405 Cov.: 32 AF XY: 0.581 AC XY: 43134 AN XY: 74264

Gnomad4 AFR AF: 0.490

Gnomad4 AMR AF: 0.624

Gnomad4 ASJ AF: 0.642

Gnomad4 EAS AF: 0.692

Gnomad4 SAS AF: 0.597

Gnomad4 FIN AF: 0.550

Gnomad4 NFE AF: 0.627

Gnomad4 OTH AF: 0.629

Alfa AF: 0.620 Hom.: 48144

Bravo AF: 0.589

Asia WGS AF: 0.634 AC: 2203 AN: 3478

EpiCase AF: 0.619

EpiControl AF: 0.625

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 11, 2014	- -

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 10, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.026
DANN	Benign	0.48

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

Other links and lift over

dbSNP: rs797821; hg19: chr7-83590852;