Variant 6-32584361-G-GTA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_002124.4(HLA-DRB1):c.117_118insTA(p.Pro40TyrfsTer41) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.33 ( 1764 hom., cov: 0)

Exomes 𝑓: 0.24 ( 24327 hom. )

Failed GnomAD Quality Control

Consequence

HLA-DRB1
NM_002124.4 frameshift

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.35

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 Benign. Variant got -10 ACMG points.

BP6

Variant 6-32584361-G-GTA is Benign according to our data. Variant chr6-32584361-G-GTA is described in ClinVar as [Likely_benign]. Clinvar id is 3059842.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-DRB1	NM_002124.4 linkuse as main transcript	c.117_118insTA	p.Pro40TyrfsTer41	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.117_118insTA	p.Pro40TyrfsTer41	frameshift_variant	2/6		NM_002124.4	P1

Frequencies

GnomAD3 genomes

AF:

0.327

AC:

23349

AN:

71482

Hom.:

1763

Cov.:

show subpopulations

Gnomad AFR

AF:

0.382

Gnomad AMI

AF:

0.217

Gnomad AMR

AF:

0.370

Gnomad ASJ

AF:

0.356

Gnomad EAS

AF:

0.323

Gnomad SAS

AF:

0.245

Gnomad FIN

AF:

0.308

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.288

Gnomad OTH

AF:

0.351

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.235

AC:

159552

AN:

678578

Hom.:

24327

Cov.:

AF XY:

0.243

AC XY:

85596

AN XY:

351856

show subpopulations

Gnomad4 AFR exome

AF:

0.356

Gnomad4 AMR exome

AF:

0.439

Gnomad4 ASJ exome

AF:

0.383

Gnomad4 EAS exome

AF:

0.333

Gnomad4 SAS exome

AF:

0.276

Gnomad4 FIN exome

AF:

0.334

Gnomad4 NFE exome

AF:

0.192

Gnomad4 OTH exome

AF:

0.258

GnomAD4 genome

AF:

0.327

AC:

23381

AN:

71564

Hom.:

1764

Cov.:

AF XY:

0.327

AC XY:

11277

AN XY:

34520

show subpopulations

Gnomad4 AFR

AF:

0.382

Gnomad4 AMR

AF:

0.371

Gnomad4 ASJ

AF:

0.356

Gnomad4 EAS

AF:

0.323

Gnomad4 SAS

AF:

0.244

Gnomad4 FIN

AF:

0.308

Gnomad4 NFE

AF:

0.288

Gnomad4 OTH

AF:

0.349

Alfa

AF:

0.398

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

HLA-DRB1-related disorder

Benign:1

Likely benign, criteria provided, single submitter

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

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