Variant 6-32584178-G-GCT details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002124.4(HLA-DRB1):c.300_301insAG(p.Arg101SerfsTer29) 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 0.21 ( 1045 hom., cov: 17)

Exomes 𝑓: 0.25 ( 27706 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: -1.09

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 6-32584178-G-GCT is Benign according to our data. Variant chr6-32584178-G-GCT is described in ClinVar as [Likely_benign]. Clinvar id is 3056296.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.217 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.300_301insAG	p.Arg101SerfsTer29	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.300_301insAG	p.Arg101SerfsTer29	frameshift_variant	2/6		NM_002124.4	P1

Frequencies

GnomAD3 genomes

AF:

0.206

AC:

9548

AN:

46288

Hom.:

1041

Cov.:

show subpopulations

Gnomad AFR

AF:

0.223

Gnomad AMI

AF:

0.0509

Gnomad AMR

AF:

0.225

Gnomad ASJ

AF:

0.316

Gnomad EAS

AF:

0.0503

Gnomad SAS

AF:

0.133

Gnomad FIN

AF:

0.161

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.208

Gnomad OTH

AF:

0.218

GnomAD3 exomes

AF:

0.141

AC:

16882

AN:

119968

Hom.:

5531

AF XY:

0.147

AC XY:

9787

AN XY:

66372

show subpopulations

Gnomad AFR exome

AF:

0.219

Gnomad AMR exome

AF:

0.0833

Gnomad ASJ exome

AF:

0.272

Gnomad EAS exome

AF:

0.0209

Gnomad SAS exome

AF:

0.143

Gnomad FIN exome

AF:

0.156

Gnomad NFE exome

AF:

0.145

Gnomad OTH exome

AF:

0.146

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.253

AC:

133515

AN:

528456

Hom.:

27706

Cov.:

AF XY:

0.257

AC XY:

67614

AN XY:

263528

show subpopulations

Gnomad4 AFR exome

AF:

0.332

Gnomad4 AMR exome

AF:

0.222

Gnomad4 ASJ exome

AF:

0.376

Gnomad4 EAS exome

AF:

0.132

Gnomad4 SAS exome

AF:

0.290

Gnomad4 FIN exome

AF:

0.267

Gnomad4 NFE exome

AF:

0.246

Gnomad4 OTH exome

AF:

0.269

GnomAD4 genome

AF:

0.206

AC:

9562

AN:

46336

Hom.:

1045

Cov.:

AF XY:

0.201

AC XY:

4537

AN XY:

22624

show subpopulations

Gnomad4 AFR

AF:

0.224

Gnomad4 AMR

AF:

0.224

Gnomad4 ASJ

AF:

0.316

Gnomad4 EAS

AF:

0.0516

Gnomad4 SAS

AF:

0.132

Gnomad4 FIN

AF:

0.161

Gnomad4 NFE

AF:

0.208

Gnomad4 OTH

AF:

0.212

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

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