Variant 9-89378917-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_001371194.2(SEMA4D):c.2376G>A(p.Thr792=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00234 in 1,614,222 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 7 hom. )

Consequence

SEMA4D
NM_001371194.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -4.22

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 9-89378917-C-T is Benign according to our data. Variant chr9-89378917-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 710800.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.22 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA4D	NM_001371194.2 linkuse as main transcript	c.2376G>A	p.Thr792=	synonymous_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.2376G>A	p.Thr792=	synonymous_variant	16/16	1	NM_001371194.2	P1	Q92854-1

Frequencies

GnomAD3 genomes

AF:

0.00160

AC:

244

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00241

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00172

AC:

433

AN:

251396

Hom.:

AF XY:

0.00171

AC XY:

232

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.00147

Gnomad ASJ exome

AF:

0.00298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000457

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00274

Gnomad OTH exome

AF:

0.00228

GnomAD4 exome

AF:

0.00242

AC:

3533

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00232

AC XY:

1685

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.00179

Gnomad4 ASJ exome

AF:

0.00295

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000336

Gnomad4 FIN exome

AF:

0.000262

Gnomad4 NFE exome

AF:

0.00283

Gnomad4 OTH exome

AF:

0.00235

GnomAD4 genome

AF:

0.00160

AC:

244

AN:

152330

Hom.:

Cov.:

AF XY:

0.00136

AC XY:

101

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.000553

Gnomad4 AMR

AF:

0.00261

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00241

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00192

Hom.:

Bravo

AF:

0.00159

EpiCase

AF:

0.00322

EpiControl

AF:

0.00332

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2024	SEMA4D: BP4, BP7 -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -

SEMA4D-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 13, 2019

This variant is classified as likely 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

-0.77

CADD

Benign

1.2

DANN

Benign

0.48

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