Variant chr6-32584360-G-GA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP6

The NM_002124.4(HLA-DRB1):c.118_119insT(p.Pro40LeufsTer2) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.29 ( 1858 hom., cov: 11)

Exomes 𝑓: 0.25 ( 26799 hom. )

Failed GnomAD Quality Control

Consequence

HLA-DRB1
NM_002124.4 frameshift

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -10.4

Variant links:

Genes affected

HLA-DRB1 (HGNC:4948): (major histocompatibility complex, class II, DR beta 1) HLA-DRB1 belongs to the HLA class II beta chain paralogs. The class II molecule is a heterodimer consisting of an alpha (DRA) and a beta chain (DRB), both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells. The beta chain is approximately 26-28 kDa. It is encoded by 6 exons. Exon one encodes the leader peptide; exons 2 and 3 encode the two extracellular domains; exon 4 encodes the transmembrane domain; and exon 5 encodes the cytoplasmic tail. Within the DR molecule the beta chain contains all the polymorphisms specifying the peptide binding specificities. Hundreds of DRB1 alleles have been described and some alleles have increased frequencies associated with certain diseases or conditions. For example, DRB1*1302 has been related to acute and chronic hepatitis B virus persistence. There are multiple pseudogenes of this gene. [provided by RefSeq, Jul 2020]

HLA-DRB1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP6

Variant 6-32584360-G-GA is Benign according to our data. Variant chr6-32584360-G-GA is described in ClinVar as [Likely_benign]. Clinvar id is 3059269.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-DRB1	NM_002124.4 linkuse as main transcript	c.118_119insT	p.Pro40LeufsTer2	frameshift_variant	2/6	ENST00000360004.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-DRB1	ENST00000360004.6 linkuse as main transcript	c.118_119insT	p.Pro40LeufsTer2	frameshift_variant	2/6		NM_002124.4	P1

Frequencies

GnomAD3 genomes

AF:

0.293

AC:

23427

AN:

79992

Hom.:

1856

Cov.:

show subpopulations

Gnomad AFR

AF:

0.342

Gnomad AMI

AF:

0.185

Gnomad AMR

AF:

0.339

Gnomad ASJ

AF:

0.328

Gnomad EAS

AF:

0.278

Gnomad SAS

AF:

0.204

Gnomad FIN

AF:

0.271

Gnomad MID

AF:

0.384

Gnomad NFE

AF:

0.260

Gnomad OTH

AF:

0.316

GnomAD3 exomes

AF:

0.181

AC:

13599

AN:

74940

Hom.:

5254

AF XY:

0.186

AC XY:

7790

AN XY:

41846

show subpopulations

Gnomad AFR exome

AF:

0.0955

Gnomad AMR exome

AF:

0.271

Gnomad ASJ exome

AF:

0.465

Gnomad EAS exome

AF:

0.0787

Gnomad SAS exome

AF:

0.217

Gnomad FIN exome

AF:

0.149

Gnomad NFE exome

AF:

0.145

Gnomad OTH exome

AF:

0.225

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.251

AC:

167169

AN:

665984

Hom.:

26799

Cov.:

AF XY:

0.259

AC XY:

89609

AN XY:

345748

show subpopulations

Gnomad4 AFR exome

AF:

0.358

Gnomad4 AMR exome

AF:

0.474

Gnomad4 ASJ exome

AF:

0.410

Gnomad4 EAS exome

AF:

0.351

Gnomad4 SAS exome

AF:

0.289

Gnomad4 FIN exome

AF:

0.348

Gnomad4 NFE exome

AF:

0.207

Gnomad4 OTH exome

AF:

0.274

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.293

AC:

23459

AN:

80094

Hom.:

1858

Cov.:

AF XY:

0.292

AC XY:

11269

AN XY:

38658

show subpopulations

Gnomad4 AFR

AF:

0.342

Gnomad4 AMR

AF:

0.339

Gnomad4 ASJ

AF:

0.328

Gnomad4 EAS

AF:

0.278

Gnomad4 SAS

AF:

0.202

Gnomad4 FIN

AF:

0.271

Gnomad4 NFE

AF:

0.260

Gnomad4 OTH

AF:

0.315

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

HLA-DRB1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 17, 2020

This variant is classified as likely 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)

0.030

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