Variant 2-74656623-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000357877.7(SEMA4F):c.235G>A(p.Val79Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0072 in 1,614,128 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0049 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0074 ( 54 hom. )

Consequence

SEMA4F
ENST00000357877.7 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.83

Variant links:

Genes affected

SEMA4F (HGNC:10734): (ssemaphorin 4F) This gene encodes a transmembrane class IV semaphorin family protein, which plays a role in neural development. This gene may be involved in neurogenesis in prostate cancer, the development of neurofibromas, and breast cancer tumorigenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2012]

SEMA4F links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013487935).

BP6

Variant 2-74656623-G-A is Benign according to our data. Variant chr2-74656623-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2651079.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA4F	NM_004263.5 link	c.235G>A	p.Val79Ile	missense_variant	2/14	ENST00000357877.7	NP_004254.2	O95754-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA4F	ENST00000357877.7 link	c.235G>A	p.Val79Ile	missense_variant	2/14	1	NM_004263.5	ENSP00000350547.2		O95754-1

Frequencies

GnomAD3 genomes

AF:

0.00490

AC:

745

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00145

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00347

Gnomad ASJ

AF:

0.00864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00943

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00715

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00501

AC:

1261

AN:

251494

Hom.:

AF XY:

0.00494

AC XY:

671

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.00154

Gnomad AMR exome

AF:

0.00272

Gnomad ASJ exome

AF:

0.0106

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00167

Gnomad FIN exome

AF:

0.00702

Gnomad NFE exome

AF:

0.00701

Gnomad OTH exome

AF:

0.00570

GnomAD4 exome

AF:

0.00744

AC:

10874

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00720

AC XY:

5235

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00128

Gnomad4 AMR exome

AF:

0.00279

Gnomad4 ASJ exome

AF:

0.0103

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00177

Gnomad4 FIN exome

AF:

0.00715

Gnomad4 NFE exome

AF:

0.00852

Gnomad4 OTH exome

AF:

0.00672

GnomAD4 genome

AF:

0.00489

AC:

745

AN:

152252

Hom.:

Cov.:

AF XY:

0.00500

AC XY:

372

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00144

Gnomad4 AMR

AF:

0.00346

Gnomad4 ASJ

AF:

0.00864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00943

Gnomad4 NFE

AF:

0.00716

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.00690

Hom.:

Bravo

AF:

0.00460

TwinsUK

AF:

0.00701

AC:

ALSPAC

AF:

0.00752

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00767

AC:

ExAC

AF:

0.00513

AC:

623

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00687

EpiControl

AF:

0.00599

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

SEMA4F: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.047

T;.;.;.;.

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.71

T;T;T;T;T

MetaRNN

Benign

0.013

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;.;L;.;.

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.39

N;.;N;N;N

REVEL

Benign

0.049

Sift

Benign

0.071

T;.;T;T;T

Sift4G

Benign

0.071

T;T;D;D;D

Polyphen

0.97

D;.;B;B;.

Vest4

0.39

MVP

0.095

MPC

0.73

ClinPred

0.020

GERP RS

3.1

Varity_R

0.069

gMVP

0.31

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