Variant 9-89379111-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001371194.2(SEMA4D):c.2182C>T(p.Leu728Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 1,614,178 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0065 ( 11 hom., cov: 32)

Exomes 𝑓: 0.00067 ( 11 hom. )

Consequence

SEMA4D
NM_001371194.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.53

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=0.007683456).

BP6

Variant 9-89379111-G-A is Benign according to our data. Variant chr9-89379111-G-A is described in ClinVar as [Benign]. Clinvar id is 3044594.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00651 (991/152294) while in subpopulation AFR AF= 0.0224 (931/41558). AF 95% confidence interval is 0.0212. There are 11 homozygotes in gnomad4. There are 471 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA4D	NM_001371194.2 linkuse as main transcript	c.2182C>T	p.Leu728Phe	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.2182C>T	p.Leu728Phe	missense_variant	16/16	1	NM_001371194.2	P1	Q92854-1

Frequencies

GnomAD3 genomes

AF:

0.00652

AC:

992

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0225

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00174

AC:

437

AN:

251364

Hom.:

AF XY:

0.00141

AC XY:

192

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.0231

Gnomad AMR exome

AF:

0.00133

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.000672

AC:

982

AN:

1461884

Hom.:

Cov.:

AF XY:

0.000587

AC XY:

427

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.0243

Gnomad4 AMR exome

AF:

0.00148

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000153

Gnomad4 OTH exome

AF:

0.00126

GnomAD4 genome

AF:

0.00651

AC:

991

AN:

152294

Hom.:

Cov.:

AF XY:

0.00632

AC XY:

471

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0224

Gnomad4 AMR

AF:

0.00314

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00114

Hom.:

Bravo

AF:

0.00784

ESP6500AA

AF:

0.0193

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00207

AC:

251

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

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

Jan 29, 2020

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

0.13

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

T;T;T;T

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.74

.;.;T;.

MetaRNN

Benign

0.0077

T;T;T;T

MetaSVM

Benign

-0.32

MutationAssessor

Uncertain

2.4

M;M;M;M

MutationTaster

Benign

0.81

D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.99

N;N;N;N

REVEL

Uncertain

0.37

Sift

Uncertain

0.0050

D;D;D;D

Sift4G

Uncertain

0.051

T;T;T;T

Polyphen

1.0

D;D;D;D

Vest4

0.35

MVP

0.51

MPC

0.90

ClinPred

0.017

GERP RS

4.5

Varity_R

0.063

gMVP

0.65

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