Variant chr6-32581554-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002124.4(HLA-DRB1):c.652+3G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00010 ( 0 hom., cov: 10)

Exomes 𝑓: 0.00049 ( 6 hom. )

Consequence

HLA-DRB1
NM_002124.4 splice_donor_region, intron

Scores

Splicing: ADA: 0.00001678

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.828

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.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 6-32581554-C-T is Benign according to our data. Variant chr6-32581554-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2656459.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-DRB1	NM_002124.4 linkuse as main transcript	c.652+3G>A		splice_donor_region_variant, intron_variant		ENST00000360004.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-DRB1	ENST00000360004.6 linkuse as main transcript	c.652+3G>A		splice_donor_region_variant, intron_variant			NM_002124.4	P1

Frequencies

GnomAD3 genomes

AF:

0.000103

AC:

AN:

77540

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000235

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000157

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000419

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000269

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00333

AC:

597

AN:

179480

Hom.:

AF XY:

0.00329

AC XY:

325

AN XY:

98676

show subpopulations

Gnomad AFR exome

AF:

0.00355

Gnomad AMR exome

AF:

0.00303

Gnomad ASJ exome

AF:

0.00170

Gnomad EAS exome

AF:

0.00326

Gnomad SAS exome

AF:

0.00819

Gnomad FIN exome

AF:

0.00299

Gnomad NFE exome

AF:

0.00217

Gnomad OTH exome

AF:

0.00424

GnomAD4 exome

AF:

0.000491

AC:

492

AN:

1001462

Hom.:

Cov.:

AF XY:

0.000622

AC XY:

315

AN XY:

506456

show subpopulations

Gnomad4 AFR exome

AF:

0.000473

Gnomad4 AMR exome

AF:

0.00110

Gnomad4 ASJ exome

AF:

0.000794

Gnomad4 EAS exome

AF:

0.000253

Gnomad4 SAS exome

AF:

0.00336

Gnomad4 FIN exome

AF:

0.000326

Gnomad4 NFE exome

AF:

0.000210

Gnomad4 OTH exome

AF:

0.000467

GnomAD4 genome

AF:

0.000103

AC:

AN:

77616

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

37288

show subpopulations

Gnomad4 AFR

AF:

0.000234

Gnomad4 AMR

AF:

0.000157

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000421

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000269

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00275

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2024

HLA-DRB1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000017

dbscSNV1_RF

Benign

0.024

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