Genetic Variant SEMA4D:p.Thr828Thr (chr9-89378809-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001371194.2(SEMA4D):c.2484G>A(p.Thr828Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0367 in 1,614,110 control chromosomes in the GnomAD database, including 1,631 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.041 ( 179 hom., cov: 33)

Exomes 𝑓: 0.036 ( 1452 hom. )

Consequence

SEMA4D
NM_001371194.2 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -3.51

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 (BayesDel_noAF=-0.7).

BP6

Variant 9-89378809-C-T is Benign according to our data. Variant chr9-89378809-C-T is described in ClinVar as [Benign]. Clinvar id is 3056145.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-3.51 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA4D	NM_001371194.2 link	c.2484G>A	p.Thr828Thr	synonymous_variant	Exon 16 of 16	ENST00000422704.7	NP_001358123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA4D	ENST00000422704.7 link	c.2484G>A	p.Thr828Thr	synonymous_variant	Exon 16 of 16	1	NM_001371194.2	ENSP00000388768.2		Q92854-1

Frequencies

GnomAD3 genomes

AF:

0.0409

AC:

6229

AN:

152132

Hom.:

179

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0583

Gnomad AMI

AF:

0.0417

Gnomad AMR

AF:

0.0243

Gnomad ASJ

AF:

0.0210

Gnomad EAS

AF:

0.0952

Gnomad SAS

AF:

0.0979

Gnomad FIN

AF:

0.0221

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0302

Gnomad OTH

AF:

0.0344

GnomAD3 exomes

AF:

0.0409

AC:

10292

AN:

251434

Hom.:

302

AF XY:

0.0430

AC XY:

5850

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.0599

Gnomad AMR exome

AF:

0.0152

Gnomad ASJ exome

AF:

0.0216

Gnomad EAS exome

AF:

0.0902

Gnomad SAS exome

AF:

0.0922

Gnomad FIN exome

AF:

0.0248

Gnomad NFE exome

AF:

0.0295

Gnomad OTH exome

AF:

0.0327

GnomAD4 exome

AF:

0.0362

AC:

52973

AN:

1461860

Hom.:

1452

Cov.:

AF XY:

0.0380

AC XY:

27607

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.0602

Gnomad4 AMR exome

AF:

0.0159

Gnomad4 ASJ exome

AF:

0.0222

Gnomad4 EAS exome

AF:

0.128

Gnomad4 SAS exome

AF:

0.0909

Gnomad4 FIN exome

AF:

0.0235

Gnomad4 NFE exome

AF:

0.0296

Gnomad4 OTH exome

AF:

0.0405

GnomAD4 genome

AF:

0.0409

AC:

6232

AN:

152250

Hom.:

179

Cov.:

AF XY:

0.0411

AC XY:

3056

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0583

Gnomad4 AMR

AF:

0.0243

Gnomad4 ASJ

AF:

0.0210

Gnomad4 EAS

AF:

0.0952

Gnomad4 SAS

AF:

0.0971

Gnomad4 FIN

AF:

0.0221

Gnomad4 NFE

AF:

0.0302

Gnomad4 OTH

AF:

0.0341

Alfa

AF:

0.0294

Hom.:

Bravo

AF:

0.0407

Asia WGS

AF:

0.112

AC:

388

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SEMA4D-related disorder

Benign:1

Feb 23, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

-0.70

CADD

Benign

0.19

DANN

Benign

0.61

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