Variant rs2722985 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -4.85

Variant links:

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]

SEMA3E links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
SEMA3E	NM_012431.3 linkuse as main transcript	c.603G>T	p.Ala201=	synonymous_variant	6/17	ENST00000643230.2	NP_036563.1
SEMA3E	NM_001178129.2 linkuse as main transcript	c.423G>T	p.Ala141=	synonymous_variant	6/17		NP_001171600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA3E	ENST00000643230.2 linkuse as main transcript	c.603G>T	p.Ala201=	synonymous_variant	6/17		NM_012431.3	ENSP00000496491	P1	O15041-1

Frequencies

GnomAD3 genomes

AF:

0.508

AC:

77125

AN:

151964

Hom.:

22439

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.604

AC XY:

439322

AN XY:

726802

show subpopulations

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.:

AF XY:

0.517

AC XY:

38452

AN XY:

74334

show subpopulations

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:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

CHARGE syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 30, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

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