Variant 15-74411588-T-C 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.1545A>G(p.Gln515=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 1,588,012 control chromosomes in the GnomAD database, including 83,786 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.39 ( 14129 hom., cov: 32)

Exomes 𝑓: 0.29 ( 69657 hom. )

Consequence

SEMA7A
NM_003612.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.37

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 15-74411588-T-C is Benign according to our data. Variant chr15-74411588-T-C is described in ClinVar as [Benign]. Clinvar id is 3060979.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-1.37 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SEMA7A	NM_003612.5 linkuse as main transcript	c.1545A>G	p.Gln515=	synonymous_variant	12/14	ENST00000261918.9
SEMA7A	NM_001146029.3 linkuse as main transcript	c.1503A>G	p.Gln501=	synonymous_variant	11/13
SEMA7A	NM_001146030.3 linkuse as main transcript	c.1050A>G	p.Gln350=	synonymous_variant	12/14
SEMA7A	XM_047433177.1 linkuse as main transcript	c.1422A>G	p.Gln474=	synonymous_variant	12/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA7A	ENST00000261918.9 linkuse as main transcript	c.1545A>G	p.Gln515=	synonymous_variant	12/14	1	NM_003612.5	P1	O75326-1
SEMA7A	ENST00000543145.6 linkuse as main transcript	c.1503A>G	p.Gln501=	synonymous_variant	11/13	2			O75326-2
SEMA7A	ENST00000542748.6 linkuse as main transcript	c.1050A>G	p.Gln350=	synonymous_variant	12/14	5
SEMA7A	ENST00000569617.1 linkuse as main transcript	n.52A>G		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

AF:

0.391

AC:

59446

AN:

151898

Hom.:

14084

Cov.:

show subpopulations

Gnomad AFR

AF:

0.655

Gnomad AMI

AF:

0.414

Gnomad AMR

AF:

0.305

Gnomad ASJ

AF:

0.275

Gnomad EAS

AF:

0.546

Gnomad SAS

AF:

0.535

Gnomad FIN

AF:

0.227

Gnomad MID

AF:

0.396

Gnomad NFE

AF:

0.261

Gnomad OTH

AF:

0.352

GnomAD3 exomes

AF:

0.347

AC:

80691

AN:

232822

Hom.:

16352

AF XY:

0.346

AC XY:

43488

AN XY:

125586

show subpopulations

Gnomad AFR exome

AF:

0.664

Gnomad AMR exome

AF:

0.324

Gnomad ASJ exome

AF:

0.273

Gnomad EAS exome

AF:

0.556

Gnomad SAS exome

AF:

0.525

Gnomad FIN exome

AF:

0.228

Gnomad NFE exome

AF:

0.255

Gnomad OTH exome

AF:

0.304

GnomAD4 exome

AF:

0.295

AC:

422985

AN:

1435996

Hom.:

69657

Cov.:

AF XY:

0.299

AC XY:

213087

AN XY:

711824

show subpopulations

Gnomad4 AFR exome

AF:

0.674

Gnomad4 AMR exome

AF:

0.319

Gnomad4 ASJ exome

AF:

0.276

Gnomad4 EAS exome

AF:

0.516

Gnomad4 SAS exome

AF:

0.517

Gnomad4 FIN exome

AF:

0.225

Gnomad4 NFE exome

AF:

0.259

Gnomad4 OTH exome

AF:

0.329

GnomAD4 genome

AF:

0.392

AC:

59562

AN:

152016

Hom.:

14129

Cov.:

AF XY:

0.393

AC XY:

29212

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.656

Gnomad4 AMR

AF:

0.305

Gnomad4 ASJ

AF:

0.275

Gnomad4 EAS

AF:

0.546

Gnomad4 SAS

AF:

0.537

Gnomad4 FIN

AF:

0.227

Gnomad4 NFE

AF:

0.261

Gnomad4 OTH

AF:

0.357

Alfa

AF:

0.275

Hom.:

10570

Bravo

AF:

0.406

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 17, 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

-0.91

CADD

Benign

8.9

DANN

Benign

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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