rs9272143

Positions:

• chr6-32633026-T-C
• chr6-32633026-T-G

Variant summary

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

The ENST00000422863.1(HLA-DQA1):​c.-39+117T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 151,194 control chromosomes in the GnomAD database, including 18,132 homozygotes. 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 0.49 (18132 hom., cov: 30)
  • Failed GnomAD Quality Control
• Consequence: HLA-DQA1 ENST00000422863.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400

Genes affected

HLA-DQA1 (HGNC:4942): (major histocompatibility complex, class II, DQ alpha 1) HLA-DQA1 belongs to the HLA class II alpha chain paralogues. The class II molecule is a heterodimer consisting of an alpha (DQA) and a beta chain (DQB), 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 (APC: B Lymphocytes, dendritic cells, macrophages). The alpha chain is approximately 33-35 kDa. It is encoded by 5 exons; exon 1 encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, and exon 4 encodes the transmembrane domain and the cytoplasmic tail. Within the DQ molecule both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to four different molecules. Typing for these polymorphisms is routinely done for bone marrow transplantation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DQA1	ENST00000422863.1	c.-39+117T>C		intron_variant				ENSP00000405797

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73501 AN: 151076 Hom.: 18119 Cov.: 30

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.456

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.529

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

GnomAD4 genome AF: 0.487 AC: 73557 AN: 151194 Hom.: 18132 Cov.: 30 AF XY: 0.485 AC XY: 35773 AN XY: 73830

Gnomad4 AFR AF: 0.463

Gnomad4 AMR AF: 0.481

Gnomad4 ASJ AF: 0.577

Gnomad4 EAS AF: 0.359

Gnomad4 SAS AF: 0.458

Gnomad4 FIN AF: 0.502

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.527

Alfa AF: 0.456 Hom.: 4215

Bravo AF: 0.479

Asia WGS AF: 0.398 AC: 1387 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.5
DANN	Benign	0.82

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9272143; hg19: chr6-32600803;