Variant 9-89379186-G-A 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.2107C>T(p.Pro703Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0593 in 1,613,992 control chromosomes in the GnomAD database, including 3,229 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.047 ( 235 hom., cov: 32)

Exomes 𝑓: 0.061 ( 2994 hom. )

Consequence

SEMA4D
NM_001371194.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.85

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=0.001972586).

BP6

Variant 9-89379186-G-A is Benign according to our data. Variant chr9-89379186-G-A is described in ClinVar as [Benign]. Clinvar id is 3056239.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0921 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.2107C>T	p.Pro703Ser	missense_variant	16/16	ENST00000422704.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA4D	ENST00000422704.7 linkuse as main transcript	c.2107C>T	p.Pro703Ser	missense_variant	16/16	1	NM_001371194.2	P1	Q92854-1

Frequencies

GnomAD3 genomes

AF:

0.0467

AC:

7102

AN:

152028

Hom.:

234

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00991

Gnomad AMI

AF:

0.0451

Gnomad AMR

AF:

0.0403

Gnomad ASJ

AF:

0.0887

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0992

Gnomad FIN

AF:

0.0729

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0639

Gnomad OTH

AF:

0.0492

GnomAD3 exomes

AF:

0.0578

AC:

14524

AN:

251420

Hom.:

534

AF XY:

0.0621

AC XY:

8439

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.00861

Gnomad AMR exome

AF:

0.0236

Gnomad ASJ exome

AF:

0.0960

Gnomad EAS exome

AF:

0.000544

Gnomad SAS exome

AF:

0.0969

Gnomad FIN exome

AF:

0.0706

Gnomad NFE exome

AF:

0.0674

Gnomad OTH exome

AF:

0.0690

GnomAD4 exome

AF:

0.0606

AC:

88588

AN:

1461846

Hom.:

2994

Cov.:

AF XY:

0.0624

AC XY:

45375

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00809

Gnomad4 AMR exome

AF:

0.0247

Gnomad4 ASJ exome

AF:

0.0939

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.0983

Gnomad4 FIN exome

AF:

0.0724

Gnomad4 NFE exome

AF:

0.0615

Gnomad4 OTH exome

AF:

0.0593

GnomAD4 genome

AF:

0.0467

AC:

7101

AN:

152146

Hom.:

235

Cov.:

AF XY:

0.0483

AC XY:

3595

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.00988

Gnomad4 AMR

AF:

0.0403

Gnomad4 ASJ

AF:

0.0887

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.0995

Gnomad4 FIN

AF:

0.0729

Gnomad4 NFE

AF:

0.0639

Gnomad4 OTH

AF:

0.0487

Alfa

AF:

0.0605

Hom.:

456

Bravo

AF:

0.0415

TwinsUK

AF:

0.0604

AC:

224

ALSPAC

AF:

0.0553

AC:

213

ESP6500AA

AF:

0.0134

AC:

ESP6500EA

AF:

0.0677

AC:

582

ExAC

AF:

0.0600

AC:

7288

Asia WGS

AF:

0.0380

AC:

131

AN:

3478

EpiCase

AF:

0.0676

EpiControl

AF:

0.0675

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

Feb 22, 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

0.066

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.30

DEOGEN2

Benign

0.11

T;T;T;T

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.50

.;.;T;.

MetaRNN

Benign

0.0020

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

L;L;L;L

MutationTaster

Benign

1.0

P;P;P;P;P;P;P;P

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.18

N;N;N;N

REVEL

Benign

0.075

Sift

Benign

0.84

T;T;T;T

Sift4G

Benign

0.31

T;T;T;T

Polyphen

0.0080

B;B;B;B

Vest4

0.031

MPC

0.24

ClinPred

0.0082

GERP RS

0.32

Varity_R

0.017

gMVP

0.36

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