Variant 6-31356245-TCC-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_005514.8(HLA-B):c.539_540del(p.Arg180GlnfsTer27) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. R180R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.030 ( 119 hom., cov: 4)

Exomes 𝑓: 0.10 ( 11708 hom. )

Failed GnomAD Quality Control

Consequence

HLA-B
NM_005514.8 frameshift

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.09

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 6-31356245-TCC-T is Benign according to our data. Variant chr6-31356245-TCC-T is described in ClinVar as [Benign]. Clinvar id is 3059333.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0301 (1432/47584) while in subpopulation NFE AF= 0.0367 (912/24874). AF 95% confidence interval is 0.0347. There are 119 homozygotes in gnomad4. There are 612 alleles in male gnomad4 subpopulation. Median coverage is 4. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1432 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-B	NM_005514.8 linkuse as main transcript	c.539_540del	p.Arg180GlnfsTer27	frameshift_variant	3/8	ENST00000412585.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-B	ENST00000412585.7 linkuse as main transcript	c.539_540del	p.Arg180GlnfsTer27	frameshift_variant	3/8		NM_005514.8	P1

Frequencies

GnomAD3 genomes

AF:

0.0301

AC:

1433

AN:

47576

Hom.:

119

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0321

Gnomad AMI

AF:

0.0306

Gnomad AMR

AF:

0.0179

Gnomad ASJ

AF:

0.0339

Gnomad EAS

AF:

0.00192

Gnomad SAS

AF:

0.0232

Gnomad FIN

AF:

0.0110

Gnomad MID

AF:

0.0652

Gnomad NFE

AF:

0.0367

Gnomad OTH

AF:

0.0270

GnomAD3 exomes

AF:

0.135

AC:

30959

AN:

228644

Hom.:

1733

AF XY:

0.139

AC XY:

17382

AN XY:

124608

show subpopulations

Gnomad AFR exome

AF:

0.142

Gnomad AMR exome

AF:

0.0790

Gnomad ASJ exome

AF:

0.0986

Gnomad EAS exome

AF:

0.0111

Gnomad SAS exome

AF:

0.114

Gnomad FIN exome

AF:

0.111

Gnomad NFE exome

AF:

0.189

Gnomad OTH exome

AF:

0.139

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.103

AC:

113729

AN:

1101466

Hom.:

11708

AF XY:

0.103

AC XY:

56779

AN XY:

549480

show subpopulations

Gnomad4 AFR exome

AF:

0.0938

Gnomad4 AMR exome

AF:

0.0562

Gnomad4 ASJ exome

AF:

0.0838

Gnomad4 EAS exome

AF:

0.00460

Gnomad4 SAS exome

AF:

0.0870

Gnomad4 FIN exome

AF:

0.0679

Gnomad4 NFE exome

AF:

0.113

Gnomad4 OTH exome

AF:

0.109

GnomAD4 genome

AF:

0.0301

AC:

1432

AN:

47584

Hom.:

119

Cov.:

AF XY:

0.0268

AC XY:

612

AN XY:

22810

show subpopulations

Gnomad4 AFR

AF:

0.0321

Gnomad4 AMR

AF:

0.0179

Gnomad4 ASJ

AF:

0.0339

Gnomad4 EAS

AF:

0.00193

Gnomad4 SAS

AF:

0.0236

Gnomad4 FIN

AF:

0.0110

Gnomad4 NFE

AF:

0.0367

Gnomad4 OTH

AF:

0.0266

Alfa

AF:

0.187

Hom.:

231

Asia WGS

AF:

0.0650

AC:

227

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

HLA-B-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 17, 2020

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

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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