Variant 9-89376952-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001142287.2(SEMA4D):c.1763C>T(p.Pro588Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00253 in 1,550,636 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0026 ( 7 hom. )

Consequence

SEMA4D
NM_001142287.2 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.65

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:

SEMA4D (HGNC:):

SEMA4D links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00844124).

BP6

Variant 9-89376952-G-A is Benign according to our data. Variant chr9-89376952-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3041927.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 7 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein	UniProt
SEMA4D	NM_001142287.2 linkuse as main transcript	c.1763C>T	p.Pro588Leu	missense_variant	18/21	NP_001135759.1	Q92854-2
SEMA4D	NM_001371198.1 linkuse as main transcript	c.1763C>T	p.Pro588Leu	missense_variant	16/19	NP_001358127.1
SEMA4D	NM_001371199.1 linkuse as main transcript	c.1763C>T	p.Pro588Leu	missense_variant	17/20	NP_001358128.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	UniProt
SEMA4D	ENST00000450295 linkuse as main transcript	c.*1752C>T		3_prime_UTR_variant	16/16	1	ENSP00000416523.1	Q92854-1
SEMA4D	ENST00000339861.8 linkuse as main transcript	c.1763C>T	p.Pro588Leu	missense_variant	16/19	5	ENSP00000344923.4	Q92854-2
SEMA4D	ENST00000420987.5 linkuse as main transcript	c.1763C>T	p.Pro588Leu	missense_variant	17/20	5	ENSP00000391733.1	Q92854-2

Frequencies

GnomAD3 genomes

AF:

0.00156

AC:

237

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000719

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:

0.00285

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00138

AC:

211

AN:

152964

Hom.:

AF XY:

0.00125

AC XY:

102

AN XY:

81438

show subpopulations

Gnomad AFR exome

AF:

0.000653

Gnomad AMR exome

AF:

0.000811

Gnomad ASJ exome

AF:

0.000118

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000131

Gnomad NFE exome

AF:

0.00287

Gnomad OTH exome

AF:

0.00323

GnomAD4 exome

AF:

0.00264

AC:

3687

AN:

1398332

Hom.:

Cov.:

AF XY:

0.00255

AC XY:

1760

AN XY:

689676

show subpopulations

Gnomad4 AFR exome

AF:

0.000348

Gnomad4 AMR exome

AF:

0.00104

Gnomad4 ASJ exome

AF:

0.000119

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000145

Gnomad4 NFE exome

AF:

0.00324

Gnomad4 OTH exome

AF:

0.00214

GnomAD4 genome

AF:

0.00156

AC:

237

AN:

152304

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000601

Gnomad4 AMR

AF:

0.000718

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00285

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00279

Hom.:

Bravo

AF:

0.00162

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00285

AC:

ExAC

AF:

0.000673

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SEMA4D-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 31, 2023

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_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.42

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.50

.;T;.

M_CAP

Benign

0.0030

MetaRNN

Benign

0.0084

T;T;T

MetaSVM

Benign

-1.0

PROVEAN

Benign

-0.040

N;N;N

REVEL

Benign

0.021

Sift

Benign

0.12

T;T;T

Sift4G

Benign

0.39

T;T;T

Polyphen

0.0020

B;B;B

Vest4

0.31

MVP

0.068

ClinPred

0.0028

GERP RS

0.42

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