Variant chr6-32584283-A-AG details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002124.4(HLA-DRB1):c.195_196insC(p.Ser66LeufsTer21) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0137 in 1,397,956 control chromosomes in the GnomAD database, including 745 homozygotes. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.010 ( 11 hom., cov: 22)

Exomes 𝑓: 0.014 ( 734 hom. )

Consequence

HLA-DRB1
NM_002124.4 frameshift

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.31

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 -10 ACMG points.

BP6

Variant 6-32584283-A-AG is Benign according to our data. Variant chr6-32584283-A-AG is described in ClinVar as [Benign]. Clinvar id is 2499005.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0103 (1310/127282) while in subpopulation EAS AF= 0.0306 (128/4178). AF 95% confidence interval is 0.0263. There are 11 homozygotes in gnomad4. There are 626 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-DRB1	NM_002124.4 linkuse as main transcript	c.195_196insC	p.Ser66LeufsTer21	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.195_196insC	p.Ser66LeufsTer21	frameshift_variant	2/6		NM_002124.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0103

AC:

1304

AN:

127186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0173

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00448

Gnomad ASJ

AF:

0.0146

Gnomad EAS

AF:

0.0308

Gnomad SAS

AF:

0.00639

Gnomad FIN

AF:

0.0101

Gnomad MID

AF:

0.00347

Gnomad NFE

AF:

0.00620

Gnomad OTH

AF:

0.0107

GnomAD3 exomes

AF:

0.00000527

AC:

AN:

189704

Hom.:

AF XY:

0.00000957

AC XY:

AN XY:

104442

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000112

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0140

AC:

17832

AN:

1270674

Hom.:

734

Cov.:

AF XY:

0.0135

AC XY:

8589

AN XY:

637308

show subpopulations

Gnomad4 AFR exome

AF:

0.0267

Gnomad4 AMR exome

AF:

0.00433

Gnomad4 ASJ exome

AF:

0.0208

Gnomad4 EAS exome

AF:

0.0355

Gnomad4 SAS exome

AF:

0.00697

Gnomad4 FIN exome

AF:

0.0122

Gnomad4 NFE exome

AF:

0.0136

Gnomad4 OTH exome

AF:

0.0171

GnomAD4 genome

AF:

0.0103

AC:

1310

AN:

127282

Hom.:

Cov.:

AF XY:

0.0101

AC XY:

626

AN XY:

61774

show subpopulations

Gnomad4 AFR

AF:

0.0174

Gnomad4 AMR

AF:

0.00447

Gnomad4 ASJ

AF:

0.0146

Gnomad4 EAS

AF:

0.0306

Gnomad4 SAS

AF:

0.00641

Gnomad4 FIN

AF:

0.0101

Gnomad4 NFE

AF:

0.00620

Gnomad4 OTH

AF:

0.0112

Alfa

AF:

0.0501

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2024

HLA-DRB1: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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