Variant rs11526468 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001371194.2(SEMA4D):c.979G>A(p.Ala327Thr) variant causes a missense change. The variant allele was found at a frequency of 0.282 in 1,607,020 control chromosomes in the GnomAD database, including 66,595 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.23 ( 4774 hom., cov: 33)

Exomes 𝑓: 0.29 ( 61821 hom. )

Consequence

SEMA4D
NM_001371194.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.76

Variant links:

Genes affected

SEMA4D (HGNC:10732): (semaphorin 4D) Enables identical protein binding activity; semaphorin receptor binding activity; and transmembrane signaling receptor activity. Involved in several processes, including positive regulation of phosphatidylinositol 3-kinase signaling; regulation of neuron projection development; and regulation of phosphate metabolic process. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SEMA4D links:

SEMA4D (HGNC:):

SEMA4D links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002583325).

BP6

Variant 9-89388764-C-T is Benign according to our data. Variant chr9-89388764-C-T is described in ClinVar as [Benign]. Clinvar id is 3060636.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA4D	NM_001371194.2 linkuse as main transcript	c.979G>A	p.Ala327Thr	missense_variant	11/16	ENST00000422704.7	NP_001358123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA4D	ENST00000422704.7 linkuse as main transcript	c.979G>A	p.Ala327Thr	missense_variant	11/16	1	NM_001371194.2	ENSP00000388768.2		Q92854-1

Frequencies

GnomAD3 genomes

AF:

0.226

AC:

34369

AN:

152060

Hom.:

4772

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0561

Gnomad AMI

AF:

0.176

Gnomad AMR

AF:

0.255

Gnomad ASJ

AF:

0.209

Gnomad EAS

AF:

0.337

Gnomad SAS

AF:

0.266

Gnomad FIN

AF:

0.327

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.297

Gnomad OTH

AF:

0.255

GnomAD3 exomes

AF:

0.273

AC:

67540

AN:

247554

Hom.:

9646

AF XY:

0.277

AC XY:

37131

AN XY:

133940

show subpopulations

Gnomad AFR exome

AF:

0.0511

Gnomad AMR exome

AF:

0.257

Gnomad ASJ exome

AF:

0.198

Gnomad EAS exome

AF:

0.335

Gnomad SAS exome

AF:

0.272

Gnomad FIN exome

AF:

0.325

Gnomad NFE exome

AF:

0.296

Gnomad OTH exome

AF:

0.284

GnomAD4 exome

AF:

0.288

AC:

419505

AN:

1454842

Hom.:

61821

Cov.:

AF XY:

0.289

AC XY:

208678

AN XY:

722676

show subpopulations

Gnomad4 AFR exome

AF:

0.0470

Gnomad4 AMR exome

AF:

0.262

Gnomad4 ASJ exome

AF:

0.198

Gnomad4 EAS exome

AF:

0.365

Gnomad4 SAS exome

AF:

0.269

Gnomad4 FIN exome

AF:

0.318

Gnomad4 NFE exome

AF:

0.297

Gnomad4 OTH exome

AF:

0.270

GnomAD4 genome

AF:

0.226

AC:

34365

AN:

152178

Hom.:

4774

Cov.:

AF XY:

0.228

AC XY:

16944

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0560

Gnomad4 AMR

AF:

0.254

Gnomad4 ASJ

AF:

0.209

Gnomad4 EAS

AF:

0.336

Gnomad4 SAS

AF:

0.265

Gnomad4 FIN

AF:

0.327

Gnomad4 NFE

AF:

0.297

Gnomad4 OTH

AF:

0.260

Alfa

AF:

0.285

Hom.:

9584

Bravo

AF:

0.214

TwinsUK

AF:

0.285

AC:

1057

ALSPAC

AF:

0.287

AC:

1108

ESP6500AA

AF:

0.0631

AC:

278

ESP6500EA

AF:

0.289

AC:

2486

ExAC

AF:

0.270

AC:

32819

Asia WGS

AF:

0.272

AC:

945

AN:

3478

EpiCase

AF:

0.292

EpiControl

AF:

0.300

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SEMA4D-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

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

0.12

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.27

.;.;.;T;T;T;T

Eigen

Pathogenic

0.70

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.62

.;T;.;.;.;T;.

MetaRNN

Benign

0.0026

T;T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.5

M;M;M;M;M;M;M

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-2.8

D;D;D;D;D;D;D

REVEL

Benign

0.29

Sift

Benign

0.069

T;T;T;T;T;T;T

Sift4G

Uncertain

0.047

D;D;D;D;D;D;D

Polyphen

1.0

D;D;D;D;D;D;D

Vest4

0.44

MPC

0.69

ClinPred

0.020

GERP RS

4.0

Varity_R

0.64

gMVP

0.66

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