Variant chr15-74411642-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_003612.5(SEMA7A):c.1491C>T(p.Gly497=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,612,364 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0064 ( 10 hom., cov: 32)

Exomes 𝑓: 0.00066 ( 11 hom. )

Consequence

SEMA7A
NM_003612.5 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -3.48

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=-0.83).

BP6

Variant 15-74411642-G-A is Benign according to our data. Variant chr15-74411642-G-A is described in ClinVar as [Benign]. Clinvar id is 3042116.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-3.48 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00641 (976/152250) while in subpopulation AFR AF= 0.0221 (920/41544). AF 95% confidence interval is 0.021. There are 10 homozygotes in gnomad4. There are 481 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 BG,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SEMA7A	NM_003612.5 linkuse as main transcript	c.1491C>T	p.Gly497=	synonymous_variant	12/14	ENST00000261918.9
SEMA7A	NM_001146029.3 linkuse as main transcript	c.1449C>T	p.Gly483=	synonymous_variant	11/13
SEMA7A	NM_001146030.3 linkuse as main transcript	c.996C>T	p.Gly332=	synonymous_variant	12/14
SEMA7A	XM_047433177.1 linkuse as main transcript	c.1368C>T	p.Gly456=	synonymous_variant	12/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA7A	ENST00000261918.9 linkuse as main transcript	c.1491C>T	p.Gly497=	synonymous_variant	12/14	1	NM_003612.5	P1	O75326-1
SEMA7A	ENST00000543145.6 linkuse as main transcript	c.1449C>T	p.Gly483=	synonymous_variant	11/13	2			O75326-2
SEMA7A	ENST00000542748.6 linkuse as main transcript	c.996C>T	p.Gly332=	synonymous_variant	12/14	5
SEMA7A	ENST00000569617.1 linkuse as main transcript			upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00639

AC:

972

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0221

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00155

AC:

385

AN:

248786

Hom.:

AF XY:

0.00113

AC XY:

152

AN XY:

134614

show subpopulations

Gnomad AFR exome

AF:

0.0215

Gnomad AMR exome

AF:

0.000992

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000329

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000356

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000658

AC:

961

AN:

1460114

Hom.:

Cov.:

AF XY:

0.000566

AC XY:

411

AN XY:

726314

show subpopulations

Gnomad4 AFR exome

AF:

0.0238

Gnomad4 AMR exome

AF:

0.00108

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000105

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000207

Gnomad4 OTH exome

AF:

0.00133

GnomAD4 genome

AF:

0.00641

AC:

976

AN:

152250

Hom.:

Cov.:

AF XY:

0.00646

AC XY:

481

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0221

Gnomad4 AMR

AF:

0.00274

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00361

Hom.:

Bravo

AF:

0.00779

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

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

Aug 20, 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

-0.83

CADD

Benign

3.8

DANN

Benign

0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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