rs9269841

chr6-32582387-A-Gchr6-32582387-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002124.4(HLA-DRB1):c.371-549T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.80 (35760 hom., cov: 16)
• Consequence: HLA-DRB1 NM_002124.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-DRB1	NM_002124.4	c.371-549T>C		intron_variant		ENST00000360004.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-DRB1	ENST00000360004.6	c.371-549T>C		intron_variant			NM_002124.4	P1

Frequencies

GnomAD3 genomes AF: 0.800 AC: 84253 AN: 105324 Hom.: 35733 Cov.: 16

Gnomad AFR AF: 0.754

Gnomad AMI AF: 0.896

Gnomad AMR AF: 0.838

Gnomad ASJ AF: 0.909

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.876

Gnomad NFE AF: 0.815

Gnomad OTH AF: 0.840

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.800 AC: 84308 AN: 105392 Hom.: 35760 Cov.: 16 AF XY: 0.793 AC XY: 40240 AN XY: 50720

Gnomad4 AFR AF: 0.755

Gnomad4 AMR AF: 0.838

Gnomad4 ASJ AF: 0.909

Gnomad4 EAS AF: 0.761

Gnomad4 SAS AF: 0.671

Gnomad4 FIN AF: 0.802

Gnomad4 NFE AF: 0.815

Gnomad4 OTH AF: 0.831

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	1.6
Dann	Benign	0.56

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

Other links and lift over

dbSNP: rs9269841; hg19: chr6-32550164;