Variant 3-50274469-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001290060.2(SEMA3B):c.1244C>T(p.Thr415Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0409 in 1,550,080 control chromosomes in the GnomAD database, including 11,737 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.10 ( 2246 hom., cov: 33)

Exomes 𝑓: 0.034 ( 9491 hom. )

Consequence

SEMA3B
NM_001290060.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.85

Variant links:

Genes affected

SEMA3B (HGNC:10724): (semaphorin 3B) The protein encoded by this gene belongs to the class-3 semaphorin/collapsin family, whose members function in growth cone guidance during neuronal development. This family member inhibits axonal extension and has been shown to act as a tumor suppressor by inducing apoptosis. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Feb 2014]

SEMA3B links:

SEMA3B (HGNC:):

SEMA3B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.2084379E-5).

BP6

Variant 3-50274469-C-T is Benign according to our data. Variant chr3-50274469-C-T is described in ClinVar as [Benign]. Clinvar id is 3058923.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA3B	NM_001290060.2 linkuse as main transcript	c.1244C>T	p.Thr415Ile	missense_variant	11/17	ENST00000616701.5	NP_001276989.1	Q13214-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA3B	ENST00000616701.5 linkuse as main transcript	c.1244C>T	p.Thr415Ile	missense_variant	11/17	1	NM_001290060.2	ENSP00000484146.1		Q13214-1

Frequencies

GnomAD3 genomes

AF:

0.103

AC:

15665

AN:

152076

Hom.:

2244

Cov.:

show subpopulations

Gnomad AFR

AF:

0.181

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.266

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.597

Gnomad SAS

AF:

0.0207

Gnomad FIN

AF:

0.0467

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00359

Gnomad OTH

AF:

0.0856

GnomAD3 exomes

AF:

0.121

AC:

24003

AN:

197684

Hom.:

5544

AF XY:

0.101

AC XY:

10747

AN XY:

106188

show subpopulations

Gnomad AFR exome

AF:

0.178

Gnomad AMR exome

AF:

0.415

Gnomad ASJ exome

AF:

0.00418

Gnomad EAS exome

AF:

0.610

Gnomad SAS exome

AF:

0.00858

Gnomad FIN exome

AF:

0.0448

Gnomad NFE exome

AF:

0.00385

Gnomad OTH exome

AF:

0.0651

GnomAD4 exome

AF:

0.0341

AC:

47692

AN:

1397886

Hom.:

9491

Cov.:

AF XY:

0.0314

AC XY:

21698

AN XY:

690496

show subpopulations

Gnomad4 AFR exome

AF:

0.195

Gnomad4 AMR exome

AF:

0.384

Gnomad4 ASJ exome

AF:

0.00461

Gnomad4 EAS exome

AF:

0.534

Gnomad4 SAS exome

AF:

0.00997

Gnomad4 FIN exome

AF:

0.0440

Gnomad4 NFE exome

AF:

0.00167

Gnomad4 OTH exome

AF:

0.0557

GnomAD4 genome

AF:

0.103

AC:

15693

AN:

152194

Hom.:

2246

Cov.:

AF XY:

0.110

AC XY:

8156

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.181

Gnomad4 AMR

AF:

0.266

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.597

Gnomad4 SAS

AF:

0.0205

Gnomad4 FIN

AF:

0.0467

Gnomad4 NFE

AF:

0.00359

Gnomad4 OTH

AF:

0.0862

Alfa

AF:

0.0334

Hom.:

1174

Bravo

AF:

0.129

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.170

AC:

653

ESP6500EA

AF:

0.00509

AC:

ExAC

AF:

0.106

AC:

12791

Asia WGS

AF:

0.204

AC:

708

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SEMA3B-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 11, 2024

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.049

BayesDel_addAF

Uncertain

0.047

BayesDel_noAF

Pathogenic

0.44

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.024

T;T;.;.;T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.068

T;.;T;T;.;T

MetaRNN

Benign

0.000012

T;T;T;T;T;T

MetaSVM

Benign

-0.91

PrimateAI

Benign

0.24

Sift4G

Benign

0.70

T;T;T;T;T;T

Polyphen

0.0

B;B;B;.;.;.

Vest4

0.015

ClinPred

0.0062

GERP RS

3.4

Varity_R

0.042

gMVP

0.096

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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