Variant 9-89402909-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001371194.2(SEMA4D):c.214G>A(p.Ala72Thr) variant causes a missense change. The variant allele was found at a frequency of 0.045 in 1,613,980 control chromosomes in the GnomAD database, including 1,945 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.034 ( 127 hom., cov: 32)

Exomes 𝑓: 0.046 ( 1818 hom. )

Consequence

SEMA4D
NM_001371194.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.47

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010484457).

BP6

Variant 9-89402909-C-T is Benign according to our data. Variant chr9-89402909-C-T is described in ClinVar as [Benign]. Clinvar id is 3055397.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA4D	NM_001371194.2 linkuse as main transcript	c.214G>A	p.Ala72Thr	missense_variant	4/16	ENST00000422704.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA4D	ENST00000422704.7 linkuse as main transcript	c.214G>A	p.Ala72Thr	missense_variant	4/16	1	NM_001371194.2	P1	Q92854-1

Frequencies

GnomAD3 genomes

AF:

0.0335

AC:

5103

AN:

152128

Hom.:

127

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00893

Gnomad AMI

AF:

0.0384

Gnomad AMR

AF:

0.0321

Gnomad ASJ

AF:

0.0118

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0170

Gnomad FIN

AF:

0.0751

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0475

Gnomad OTH

AF:

0.0258

GnomAD3 exomes

AF:

0.0357

AC:

8970

AN:

251412

Hom.:

197

AF XY:

0.0359

AC XY:

4878

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.00812

Gnomad AMR exome

AF:

0.0315

Gnomad ASJ exome

AF:

0.0127

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0187

Gnomad FIN exome

AF:

0.0724

Gnomad NFE exome

AF:

0.0461

Gnomad OTH exome

AF:

0.0380

GnomAD4 exome

AF:

0.0462

AC:

67480

AN:

1461734

Hom.:

1818

Cov.:

AF XY:

0.0453

AC XY:

32908

AN XY:

727148

show subpopulations

Gnomad4 AFR exome

AF:

0.00654

Gnomad4 AMR exome

AF:

0.0311

Gnomad4 ASJ exome

AF:

0.0132

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0188

Gnomad4 FIN exome

AF:

0.0726

Gnomad4 NFE exome

AF:

0.0519

Gnomad4 OTH exome

AF:

0.0377

GnomAD4 genome

AF:

0.0335

AC:

5106

AN:

152246

Hom.:

127

Cov.:

AF XY:

0.0342

AC XY:

2542

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.00890

Gnomad4 AMR

AF:

0.0321

Gnomad4 ASJ

AF:

0.0118

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.0170

Gnomad4 FIN

AF:

0.0751

Gnomad4 NFE

AF:

0.0475

Gnomad4 OTH

AF:

0.0260

Alfa

AF:

0.0398

Hom.:

221

Bravo

AF:

0.0294

TwinsUK

AF:

0.0491

AC:

182

ALSPAC

AF:

0.0490

AC:

189

ESP6500AA

AF:

0.00794

AC:

ESP6500EA

AF:

0.0435

AC:

374

ExAC

AF:

0.0340

AC:

4134

Asia WGS

AF:

0.00635

AC:

AN:

3478

EpiCase

AF:

0.0410

EpiControl

AF:

0.0431

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

SEMA4D-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 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

0.17

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Uncertain

1.0

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.91

MetaRNN

Benign

0.010

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

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

M;M;M;M;M;M;M;.;.

MutationTaster

Benign

1.0

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

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-2.7

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

REVEL

Benign

0.14

Sift

Uncertain

0.0090

D;D;D;D;D;D;D;T;T

Sift4G

Uncertain

0.0070

D;D;D;D;D;D;D;.;.

Polyphen

0.72

P;P;P;P;P;P;P;.;.

Vest4

0.36

MPC

0.65

ClinPred

0.049

GERP RS

4.8

Varity_R

0.77

gMVP

0.50

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