6-32579276-A-T

Variant names:

• chr6-32579276-A-T
• rs9269701
• NM_002124.4:c.788-172T>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002124.4(HLA-DRB1):​c.788-172T>A 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 0.0 (0 hom., cov: 6)
  • Failed GnomAD Quality Control
• Consequence: HLA-DRB1 NM_002124.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DRB1	NM_002124.4	c.788-172T>A		intron_variant	Intron 5 of 5	ENST00000360004.6	NP_002115.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DRB1	ENST00000360004.6	c.788-172T>A		intron_variant	Intron 5 of 5	6	NM_002124.4	ENSP00000353099.5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 56058 Hom.: 0 Cov.: 6

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 56058 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 27142

African (AFR) AF: 0.00 AC: 0 AN: 13912

American (AMR) AF: 0.00 AC: 0 AN: 4538

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1088

East Asian (EAS) AF: 0.00 AC: 0 AN: 1558

South Asian (SAS) AF: 0.00 AC: 0 AN: 1698

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4846

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 88

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 27278

Other (OTH) AF: 0.00 AC: 0 AN: 666

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.0
DANN	Benign	0.17
PhyloP100		-1.1

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

Other links and lift over

dbSNP: rs9269701; hg19: chr6-32547053;