Variant 9-89376938-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The ENST00000450295.5(SEMA4D):c.*1766G>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.000428 in 1,550,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

SEMA4D
ENST00000450295.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.09

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0060606897).

BP6

Variant 9-89376938-C-A is Benign according to our data. Variant chr9-89376938-C-A is described in ClinVar as [Benign]. Clinvar id is 3049327.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons
SEMA4D	NM_001142287.2 linkuse as main transcript	c.1777G>T	p.Gly593Trp	missense_variant	18/21
SEMA4D	NM_001371198.1 linkuse as main transcript	c.1777G>T	p.Gly593Trp	missense_variant	16/19
SEMA4D	NM_001371199.1 linkuse as main transcript	c.1777G>T	p.Gly593Trp	missense_variant	17/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Appris	UniProt
SEMA4D	ENST00000450295.5 linkuse as main transcript	c.*1766G>T		3_prime_UTR_variant	16/16	1	P1	Q92854-1
SEMA4D	ENST00000339861.8 linkuse as main transcript	c.1777G>T	p.Gly593Trp	missense_variant	16/19	5		Q92854-2
SEMA4D	ENST00000420987.5 linkuse as main transcript	c.1777G>T	p.Gly593Trp	missense_variant	17/20	5		Q92854-2

Frequencies

GnomAD3 genomes

AF:

0.00236

AC:

359

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00820

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000850

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.000464

AC:

AN:

153112

Hom.:

AF XY:

0.000344

AC XY:

AN XY:

81462

show subpopulations

Gnomad AFR exome

AF:

0.00794

Gnomad AMR exome

AF:

0.000284

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000878

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000231

GnomAD4 exome

AF:

0.000217

AC:

303

AN:

1398460

Hom.:

Cov.:

AF XY:

0.000193

AC XY:

133

AN XY:

689746

show subpopulations

Gnomad4 AFR exome

AF:

0.00813

Gnomad4 AMR exome

AF:

0.000476

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000505

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000371

Gnomad4 OTH exome

AF:

0.000328

GnomAD4 genome

AF:

0.00236

AC:

360

AN:

152308

Hom.:

Cov.:

AF XY:

0.00199

AC XY:

148

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00820

Gnomad4 AMR

AF:

0.000849

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00129

Hom.:

Bravo

AF:

0.00260

ExAC

AF:

0.000422

AC:

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 28, 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_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.97

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.91

M_CAP

Benign

0.045

MetaRNN

Benign

0.0061

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

D;N;N;N;N

PROVEAN

Benign

-1.1

N;N;N

REVEL

Benign

0.17

Sift

Benign

0.032

D;D;D

Sift4G

Uncertain

0.033

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.50

MVP

0.15

ClinPred

0.067

GERP RS

3.6

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