Variant NM_005514.8:c.537_538insGA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1

The NM_005514.8(HLA-B):c.537_538insGA(p.Arg180AspfsTer35) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 1,134,496 control chromosomes in the GnomAD database, including 12,045 homozygotes. Variant has been reported in ClinVar as Benign (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.035 ( 118 hom., cov: 6)

Exomes 𝑓: 0.10 ( 11927 hom. )

Consequence

HLA-B
NM_005514.8 frameshift

Scores

Not classified

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -4.48

Variant links:

Genes affected

HLA-B (HGNC:4932): (major histocompatibility complex, class I, B) HLA-B belongs to the HLA class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. Class I molecules play a central role in the immune system by presenting peptides derived from the endoplasmic reticulum lumen. They are expressed in nearly all cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon 1 encodes the leader peptide, exon 2 and 3 encode the alpha1 and alpha2 domains, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region and exons 6 and 7 encode the cytoplasmic tail. Polymorphisms within exon 2 and exon 3 are responsible for the peptide binding specificity of each class one molecule. Typing for these polymorphisms is routinely done for bone marrow and kidney transplantation. Hundreds of HLA-B alleles have been described. [provided by RefSeq, Jul 2008]

HLA-B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 6-31356248-G-GTC is Benign according to our data. Variant chr6-31356248-G-GTC is described in ClinVar as [Benign]. Clinvar id is 3059849.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-B	NM_005514.8 link	c.537_538insGA	p.Arg180AspfsTer35	frameshift_variant	Exon 3 of 8	ENST00000412585.7	NP_005505.2	P01889E5FQ95

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-B	ENST00000412585.7 link	c.537_538insGA	p.Arg180AspfsTer35	frameshift_variant	Exon 3 of 8	6	NM_005514.8	ENSP00000399168.2		P01889

Frequencies

GnomAD3 genomes

AF:

0.0353

AC:

1441

AN:

40814

Hom.:

118

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0372

Gnomad AMI

AF:

0.0329

Gnomad AMR

AF:

0.0211

Gnomad ASJ

AF:

0.0404

Gnomad EAS

AF:

0.00159

Gnomad SAS

AF:

0.0282

Gnomad FIN

AF:

0.0128

Gnomad MID

AF:

0.0833

Gnomad NFE

AF:

0.0433

Gnomad OTH

AF:

0.0326

GnomAD3 exomes

AF:

0.138

AC:

29726

AN:

214864

Hom.:

1727

AF XY:

0.142

AC XY:

16658

AN XY:

116944

show subpopulations

Gnomad AFR exome

AF:

0.146

Gnomad AMR exome

AF:

0.0803

Gnomad ASJ exome

AF:

0.102

Gnomad EAS exome

AF:

0.0106

Gnomad SAS exome

AF:

0.122

Gnomad FIN exome

AF:

0.108

Gnomad NFE exome

AF:

0.193

Gnomad OTH exome

AF:

0.144

GnomAD4 exome

AF:

0.103

AC:

112564

AN:

1093664

Hom.:

11927

Cov.:

AF XY:

0.103

AC XY:

56170

AN XY:

545360

show subpopulations

Gnomad4 AFR exome

AF:

0.0924

Gnomad4 AMR exome

AF:

0.0558

Gnomad4 ASJ exome

AF:

0.0864

Gnomad4 EAS exome

AF:

0.00429

Gnomad4 SAS exome

AF:

0.0864

Gnomad4 FIN exome

AF:

0.0699

Gnomad4 NFE exome

AF:

0.112

Gnomad4 OTH exome

AF:

0.108

GnomAD4 genome

AF:

0.0353

AC:

1440

AN:

40832

Hom.:

118

Cov.:

AF XY:

0.0318

AC XY:

619

AN XY:

19470

show subpopulations

Gnomad4 AFR

AF:

0.0372

Gnomad4 AMR

AF:

0.0210

Gnomad4 ASJ

AF:

0.0404

Gnomad4 EAS

AF:

0.00160

Gnomad4 SAS

AF:

0.0285

Gnomad4 FIN

AF:

0.0128

Gnomad4 NFE

AF:

0.0433

Gnomad4 OTH

AF:

0.0321

Alfa

AF:

0.227

Hom.:

234

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HLA-B-related disorder

Benign:1

Dec 17, 2020

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

Splicing

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