rs2722985

chr7-83408435-C-A

Variant summary

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

The NM_012431.3(SEMA3E):c.603G>T(p.Ala201=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 1,613,168 control chromosomes in the GnomAD database, including 294,423 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (22454 hom., cov: 33)
  • Exomes 𝑓: 0.60 (271969 hom.)
• Consequence: SEMA3E NM_012431.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -4.85

Genes affected

SEMA3E (HGNC:10727): (semaphorin 3E) Semaphorins are a large family of conserved secreted and membrane associated proteins which possess a semaphorin (Sema) domain and a PSI domain (found in plexins, semaphorins and integrins) in the N-terminal extracellular portion. Based on sequence and structural similarities, semaphorins are put into eight classes: invertebrates contain classes 1 and 2, viruses have class V, and vertebrates contain classes 3-7. Semaphorins serve as axon guidance ligands via multimeric receptor complexes, some (if not all) containing plexin proteins. This gene encodes a class 4 semaphorin. This gene encodes a class 3 semaphorin. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 7-83408435-C-A is Benign according to our data. Variant chr7-83408435-C-A is described in ClinVar as [Benign]. Clinvar id is 260255.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-83408435-C-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-4.85 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA3E	NM_012431.3	c.603G>T	p.Ala201=	synonymous_variant	6/17	ENST00000643230.2
SEMA3E	NM_001178129.2	c.423G>T	p.Ala141=	synonymous_variant	6/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA3E	ENST00000643230.2	c.603G>T	p.Ala201=	synonymous_variant	6/17		NM_012431.3	P1

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77125 AN: 151964 Hom.: 22439 Cov.: 33

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.848

Gnomad SAS AF: 0.675

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.598

Gnomad OTH AF: 0.530

GnomAD3 exomes AF: 0.616 AC: 154315 AN: 250570 Hom.: 50108 AF XY: 0.617 AC XY: 83594 AN XY: 135414

Gnomad AFR exome AF: 0.200

Gnomad AMR exome AF: 0.707

Gnomad ASJ exome AF: 0.438

Gnomad EAS exome AF: 0.879

Gnomad SAS exome AF: 0.661

Gnomad FIN exome AF: 0.669

Gnomad NFE exome AF: 0.600

Gnomad OTH exome AF: 0.601

GnomAD4 exome AF: 0.604 AC: 882062 AN: 1461086 Hom.: 271969 Cov.: 45 AF XY: 0.604 AC XY: 439322 AN XY: 726802

Gnomad4 AFR exome AF: 0.190

Gnomad4 AMR exome AF: 0.700

Gnomad4 ASJ exome AF: 0.441

Gnomad4 EAS exome AF: 0.833

Gnomad4 SAS exome AF: 0.653

Gnomad4 FIN exome AF: 0.668

Gnomad4 NFE exome AF: 0.603

Gnomad4 OTH exome AF: 0.582

GnomAD4 genome AF: 0.507 AC: 77153 AN: 152082 Hom.: 22454 Cov.: 33 AF XY: 0.517 AC XY: 38452 AN XY: 74334

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.628

Gnomad4 ASJ AF: 0.444

Gnomad4 EAS AF: 0.849

Gnomad4 SAS AF: 0.675

Gnomad4 FIN AF: 0.678

Gnomad4 NFE AF: 0.598

Gnomad4 OTH AF: 0.532

Alfa AF: 0.577 Hom.: 49374

Bravo AF: 0.493

Asia WGS AF: 0.741 AC: 2577 AN: 3478

EpiCase AF: 0.587

EpiControl AF: 0.582

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

CHARGE syndrome Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	0.70
Dann	Benign	0.62

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: rs2722985; hg19: chr7-83037751; COSMIC: COSV57090572;