15-74414602-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_003612.5(SEMA7A):c.1239C>T(p.Val413=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0709 in 1,614,038 control chromosomes in the GnomAD database, including 7,675 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.14 ( 2518 hom., cov: 32)

Exomes 𝑓: 0.064 ( 5157 hom. )

Consequence

SEMA7A
NM_003612.5 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0960

Variant links:

Genes affected

SEMA7A (HGNC:10741): (semaphorin 7A (JohnMiltonHagen blood group)) This gene encodes a member of the semaphorin family of proteins. The encoded preproprotein is proteolytically processed to generate the mature glycosylphosphatidylinositol (GPI)-anchored membrane glycoprotein. The encoded protein is found on activated lymphocytes and erythrocytes and may be involved in immunomodulatory and neuronal processes. The encoded protein carries the John Milton Hagen (JMH) blood group antigens. Mutations in this gene may be associated with reduced bone mineral density (BMD). Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Feb 2016]

SEMA7A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 15-74414602-G-A is Benign according to our data. Variant chr15-74414602-G-A is described in ClinVar as [Benign]. Clinvar id is 3059177.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.096 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SEMA7A	NM_003612.5 linkuse as main transcript	c.1239C>T	p.Val413=	synonymous_variant	10/14	ENST00000261918.9
SEMA7A	NM_001146029.3 linkuse as main transcript	c.1197C>T	p.Val399=	synonymous_variant	9/13
SEMA7A	NM_001146030.3 linkuse as main transcript	c.744C>T	p.Val248=	synonymous_variant	10/14
SEMA7A	XM_047433177.1 linkuse as main transcript	c.1116C>T	p.Val372=	synonymous_variant	10/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA7A	ENST00000261918.9 linkuse as main transcript	c.1239C>T	p.Val413=	synonymous_variant	10/14	1	NM_003612.5	P1	O75326-1
SEMA7A	ENST00000543145.6 linkuse as main transcript	c.1197C>T	p.Val399=	synonymous_variant	9/13	2			O75326-2
SEMA7A	ENST00000542748.6 linkuse as main transcript	c.744C>T	p.Val248=	synonymous_variant	10/14	5

Frequencies

GnomAD3 genomes

AF:

0.135

AC:

20525

AN:

152074

Hom.:

2516

Cov.:

show subpopulations

Gnomad AFR

AF:

0.328

Gnomad AMI

AF:

0.0538

Gnomad AMR

AF:

0.0591

Gnomad ASJ

AF:

0.0323

Gnomad EAS

AF:

0.188

Gnomad SAS

AF:

0.116

Gnomad FIN

AF:

0.0783

Gnomad MID

AF:

0.0701

Gnomad NFE

AF:

0.0483

Gnomad OTH

AF:

0.109

GnomAD3 exomes

AF:

0.0857

AC:

21550

AN:

251470

Hom.:

1810

AF XY:

0.0843

AC XY:

11463

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.338

Gnomad AMR exome

AF:

0.0303

Gnomad ASJ exome

AF:

0.0335

Gnomad EAS exome

AF:

0.198

Gnomad SAS exome

AF:

0.127

Gnomad FIN exome

AF:

0.0744

Gnomad NFE exome

AF:

0.0452

Gnomad OTH exome

AF:

0.0613

GnomAD4 exome

AF:

0.0642

AC:

93888

AN:

1461846

Hom.:

5157

Cov.:

AF XY:

0.0652

AC XY:

47394

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.338

Gnomad4 AMR exome

AF:

0.0336

Gnomad4 ASJ exome

AF:

0.0338

Gnomad4 EAS exome

AF:

0.168

Gnomad4 SAS exome

AF:

0.124

Gnomad4 FIN exome

AF:

0.0700

Gnomad4 NFE exome

AF:

0.0486

Gnomad4 OTH exome

AF:

0.0772

GnomAD4 genome

AF:

0.135

AC:

20553

AN:

152192

Hom.:

2518

Cov.:

AF XY:

0.135

AC XY:

10051

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.328

Gnomad4 AMR

AF:

0.0591

Gnomad4 ASJ

AF:

0.0323

Gnomad4 EAS

AF:

0.187

Gnomad4 SAS

AF:

0.117

Gnomad4 FIN

AF:

0.0783

Gnomad4 NFE

AF:

0.0483

Gnomad4 OTH

AF:

0.108

Alfa

AF:

0.0652

Hom.:

1102

Bravo

AF:

0.140

Asia WGS

AF:

0.141

AC:

490

AN:

3478

EpiCase

AF:

0.0472

EpiControl

AF:

0.0458

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

SEMA7A-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 24, 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_noAF

Benign

-0.56

Cadd

Benign

3.4

Dann

Benign

0.69

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