Variant 9-89363868-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The ENST00000420101.6(SEMA4D):c.120C>T(p.Pro40=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 1,614,018 control chromosomes in the GnomAD database, including 20,110 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.12 ( 1777 hom., cov: 33)

Exomes 𝑓: 0.14 ( 18333 hom. )

Consequence

SEMA4D
ENST00000420101.6 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.50

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:

SECISBP2 (HGNC:):

SECISBP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 9-89363868-G-A is Benign according to our data. Variant chr9-89363868-G-A is described in ClinVar as [Benign]. Clinvar id is 3060340.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.5 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons
SEMA4D	XM_047422629.1 linkuse as main transcript	c.1529C>T	p.Pro510Leu	missense_variant	18/18
SEMA4D	NM_001142287.2 linkuse as main transcript	c.1965C>T	p.Pro655=	synonymous_variant	19/21
SEMA4D	NM_001371198.1 linkuse as main transcript	c.1965C>T	p.Pro655=	synonymous_variant	17/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	UniProt
SEMA4D	ENST00000420101.6 linkuse as main transcript	c.120C>T	p.Pro40=	synonymous_variant	1/3	1
SEMA4D	ENST00000475255.5 linkuse as main transcript	n.1787C>T		non_coding_transcript_exon_variant	1/2	1
SEMA4D	ENST00000339861.8 linkuse as main transcript	c.1965C>T	p.Pro655=	synonymous_variant	17/19	5	Q92854-2

Frequencies

GnomAD3 genomes

AF:

0.124

AC:

18808

AN:

152144

Hom.:

1769

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0311

Gnomad AMI

AF:

0.155

Gnomad AMR

AF:

0.293

Gnomad ASJ

AF:

0.0888

Gnomad EAS

AF:

0.203

Gnomad SAS

AF:

0.135

Gnomad FIN

AF:

0.141

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.135

Gnomad OTH

AF:

0.111

GnomAD3 exomes

AF:

0.176

AC:

44288

AN:

251246

Hom.:

5991

AF XY:

0.166

AC XY:

22504

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.0289

Gnomad AMR exome

AF:

0.453

Gnomad ASJ exome

AF:

0.0823

Gnomad EAS exome

AF:

0.209

Gnomad SAS exome

AF:

0.137

Gnomad FIN exome

AF:

0.152

Gnomad NFE exome

AF:

0.133

Gnomad OTH exome

AF:

0.139

GnomAD4 exome

AF:

0.145

AC:

211597

AN:

1461756

Hom.:

18333

Cov.:

AF XY:

0.143

AC XY:

103814

AN XY:

727166

show subpopulations

Gnomad4 AFR exome

AF:

0.0234

Gnomad4 AMR exome

AF:

0.434

Gnomad4 ASJ exome

AF:

0.0832

Gnomad4 EAS exome

AF:

0.158

Gnomad4 SAS exome

AF:

0.135

Gnomad4 FIN exome

AF:

0.159

Gnomad4 NFE exome

AF:

0.139

Gnomad4 OTH exome

AF:

0.130

GnomAD4 genome

AF:

0.124

AC:

18828

AN:

152262

Hom.:

1777

Cov.:

AF XY:

0.127

AC XY:

9488

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0310

Gnomad4 AMR

AF:

0.294

Gnomad4 ASJ

AF:

0.0888

Gnomad4 EAS

AF:

0.203

Gnomad4 SAS

AF:

0.135

Gnomad4 FIN

AF:

0.141

Gnomad4 NFE

AF:

0.135

Gnomad4 OTH

AF:

0.112

Alfa

AF:

0.0962

Hom.:

345

Bravo

AF:

0.133

Asia WGS

AF:

0.192

AC:

665

AN:

3478

EpiCase

AF:

0.119

EpiControl

AF:

0.121

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 18, 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

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.075

DANN

Benign

0.68

Splicing

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