Variant chr15-74410681-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_003612.5(SEMA7A):c.1944C>T(p.Ala648=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0704 in 1,609,660 control chromosomes in the GnomAD database, including 7,574 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.14 ( 2533 hom., cov: 32)

Exomes 𝑓: 0.064 ( 5041 hom. )

Consequence

SEMA7A
NM_003612.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -4.95

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 15-74410681-G-A is Benign according to our data. Variant chr15-74410681-G-A is described in ClinVar as [Benign]. Clinvar id is 3059310.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-4.95 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.1944C>T	p.Ala648=	synonymous_variant	14/14	ENST00000261918.9
SEMA7A	NM_001146029.3 linkuse as main transcript	c.1902C>T	p.Ala634=	synonymous_variant	13/13
SEMA7A	NM_001146030.3 linkuse as main transcript	c.1449C>T	p.Ala483=	synonymous_variant	14/14
SEMA7A	XM_047433177.1 linkuse as main transcript	c.1821C>T	p.Ala607=	synonymous_variant	14/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA7A	ENST00000261918.9 linkuse as main transcript	c.1944C>T	p.Ala648=	synonymous_variant	14/14	1	NM_003612.5	P1	O75326-1
SEMA7A	ENST00000543145.6 linkuse as main transcript	c.1902C>T	p.Ala634=	synonymous_variant	13/13	2			O75326-2
SEMA7A	ENST00000542748.6 linkuse as main transcript	c.1449C>T	p.Ala483=	synonymous_variant	14/14	5

Frequencies

GnomAD3 genomes

AF:

0.135

AC:

20537

AN:

152164

Hom.:

2530

Cov.:

show subpopulations

Gnomad AFR

AF:

0.328

Gnomad AMI

AF:

0.0537

Gnomad AMR

AF:

0.0593

Gnomad ASJ

AF:

0.0323

Gnomad EAS

AF:

0.189

Gnomad SAS

AF:

0.108

Gnomad FIN

AF:

0.0787

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0484

Gnomad OTH

AF:

0.109

GnomAD3 exomes

AF:

0.0846

AC:

21106

AN:

249526

Hom.:

1775

AF XY:

0.0826

AC XY:

11155

AN XY:

134970

show subpopulations

Gnomad AFR exome

AF:

0.339

Gnomad AMR exome

AF:

0.0308

Gnomad ASJ exome

AF:

0.0334

Gnomad EAS exome

AF:

0.199

Gnomad SAS exome

AF:

0.116

Gnomad FIN exome

AF:

0.0745

Gnomad NFE exome

AF:

0.0452

Gnomad OTH exome

AF:

0.0613

GnomAD4 exome

AF:

0.0637

AC:

92778

AN:

1457378

Hom.:

5041

Cov.:

AF XY:

0.0643

AC XY:

46556

AN XY:

724140

show subpopulations

Gnomad4 AFR exome

AF:

0.339

Gnomad4 AMR exome

AF:

0.0340

Gnomad4 ASJ exome

AF:

0.0338

Gnomad4 EAS exome

AF:

0.169

Gnomad4 SAS exome

AF:

0.112

Gnomad4 FIN exome

AF:

0.0699

Gnomad4 NFE exome

AF:

0.0487

Gnomad4 OTH exome

AF:

0.0772

GnomAD4 genome

AF:

0.135

AC:

20564

AN:

152282

Hom.:

2533

Cov.:

AF XY:

0.135

AC XY:

10051

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.328

Gnomad4 AMR

AF:

0.0593

Gnomad4 ASJ

AF:

0.0323

Gnomad4 EAS

AF:

0.188

Gnomad4 SAS

AF:

0.109

Gnomad4 FIN

AF:

0.0787

Gnomad4 NFE

AF:

0.0484

Gnomad4 OTH

AF:

0.107

Alfa

AF:

0.0661

Hom.:

817

Bravo

AF:

0.141

Asia WGS

AF:

0.140

AC:

485

AN:

3478

EpiCase

AF:

0.0471

EpiControl

AF:

0.0457

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SEMA7A-related disorder

Benign:1

Benign, no assertion criteria provided

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

-0.87

CADD

Benign

0.79

DANN

Benign

0.31

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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