Variant chr6-32581763-C-T 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.446G>A(p.Ser149Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 1,160,604 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.18 ( 0 hom., cov: 23)

Exomes 𝑓: 0.16 ( 79 hom. )

Consequence

HLA-DRB1
NM_002124.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.59

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 6-32581763-C-T is Benign according to our data. Variant chr6-32581763-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3060198.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.25 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.446G>A	p.Ser149Asn	missense_variant	3/6	ENST00000360004.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-DRB1	ENST00000360004.6 linkuse as main transcript	c.446G>A	p.Ser149Asn	missense_variant	3/6		NM_002124.4	P1

Frequencies

GnomAD3 genomes

AF:

0.184

AC:

22612

AN:

122866

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.119

Gnomad AMI

AF:

0.271

Gnomad AMR

AF:

0.236

Gnomad ASJ

AF:

0.225

Gnomad EAS

AF:

0.262

Gnomad SAS

AF:

0.192

Gnomad FIN

AF:

0.186

Gnomad MID

AF:

0.191

Gnomad NFE

AF:

0.200

Gnomad OTH

AF:

0.187

GnomAD4 exome

AF:

0.155

AC:

161026

AN:

1037648

Hom.:

Cov.:

AF XY:

0.151

AC XY:

78686

AN XY:

519762

show subpopulations

Gnomad4 AFR exome

AF:

0.0720

Gnomad4 AMR exome

AF:

0.169

Gnomad4 ASJ exome

AF:

0.174

Gnomad4 EAS exome

AF:

0.252

Gnomad4 SAS exome

AF:

0.123

Gnomad4 FIN exome

AF:

0.167

Gnomad4 NFE exome

AF:

0.155

Gnomad4 OTH exome

AF:

0.158

GnomAD4 genome

AF:

0.184

AC:

22624

AN:

122956

Hom.:

Cov.:

AF XY:

0.184

AC XY:

11004

AN XY:

59686

show subpopulations

Gnomad4 AFR

AF:

0.119

Gnomad4 AMR

AF:

0.236

Gnomad4 ASJ

AF:

0.225

Gnomad4 EAS

AF:

0.263

Gnomad4 SAS

AF:

0.193

Gnomad4 FIN

AF:

0.186

Gnomad4 NFE

AF:

0.200

Gnomad4 OTH

AF:

0.186

Alfa

AF:

0.197

Hom.:

ExAC

AF:

0.188

AC:

22820

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

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.058

DANN

Benign

0.32

DEOGEN2

Benign

0.0088

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.033

MetaRNN

Benign

0.0027

MetaSVM

Benign

-0.93

MutationTaster

Benign

1.0

PROVEAN

Benign

-0.090

REVEL

Benign

0.020

Sift

Benign

1.0

Sift4G

Benign

0.32

Polyphen

0.0

Vest4

0.025

MPC

0.68

ClinPred

0.0020

GERP RS

0.026

Varity_R

0.13

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.23

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.23

Position offset: -15

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