Variant 6-32584351-TCCC-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PM4_Supporting

The NM_002124.4(HLA-DRB1):c.125_127del(p.Arg42_Glu43delinsLys) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0049 ( 0 hom., cov: 11)

Exomes 𝑓: 0.0092 ( 285 hom. )

Failed GnomAD Quality Control

Consequence

HLA-DRB1
NM_002124.4 inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.66

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 Uncertain_significance. Variant got 1 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_002124.4. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-DRB1	NM_002124.4 linkuse as main transcript	c.125_127del	p.Arg42_Glu43delinsLys	inframe_deletion	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.125_127del	p.Arg42_Glu43delinsLys	inframe_deletion	2/6		NM_002124.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00493

AC:

527

AN:

106882

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00381

Gnomad AMI

AF:

0.0227

Gnomad AMR

AF:

0.00420

Gnomad ASJ

AF:

0.00638

Gnomad EAS

AF:

0.00171

Gnomad SAS

AF:

0.00590

Gnomad FIN

AF:

0.00171

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00618

Gnomad OTH

AF:

0.00432

GnomAD3 exomes

AF:

0.0000193

AC:

AN:

103648

Hom.:

AF XY:

0.0000174

AC XY:

AN XY:

57588

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:

0.0000575

Gnomad FIN exome

AF:

0.000127

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00921

AC:

6837

AN:

742280

Hom.:

285

AF XY:

0.00975

AC XY:

3745

AN XY:

383954

show subpopulations

Gnomad4 AFR exome

AF:

0.00637

Gnomad4 AMR exome

AF:

0.0127

Gnomad4 ASJ exome

AF:

0.0133

Gnomad4 EAS exome

AF:

0.00152

Gnomad4 SAS exome

AF:

0.0149

Gnomad4 FIN exome

AF:

0.00550

Gnomad4 NFE exome

AF:

0.00859

Gnomad4 OTH exome

AF:

0.0104

GnomAD4 genome

AF:

0.00491

AC:

525

AN:

106982

Hom.:

Cov.:

AF XY:

0.00473

AC XY:

245

AN XY:

51812

show subpopulations

Gnomad4 AFR

AF:

0.00383

Gnomad4 AMR

AF:

0.00420

Gnomad4 ASJ

AF:

0.00638

Gnomad4 EAS

AF:

0.00171

Gnomad4 SAS

AF:

0.00528

Gnomad4 FIN

AF:

0.00171

Gnomad4 NFE

AF:

0.00616

Gnomad4 OTH

AF:

0.00425

Alfa

AF:

0.0486

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Multiple sclerosis, susceptibility to

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

Mar 29, 2024

- -

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