6-32633026-T-C

Variant names:

• chr6-32633026-T-C
• rs9272143
• ENST00000422863.1:c.-39+117T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 46 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DQA1	ENST00000422863.1	c.-39+117T>C		intron_variant	Intron 3 of 3	6		ENSP00000405797.1

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

African (AFR) AF: 0.463 AC: 19087 AN: 41196

American (AMR) AF: 0.481 AC: 7309 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 1993 AN: 3456

East Asian (EAS) AF: 0.359 AC: 1850 AN: 5158

South Asian (SAS) AF: 0.458 AC: 2187 AN: 4776

European-Finnish (FIN) AF: 0.502 AC: 5255 AN: 10460

Middle Eastern (MID) AF: 0.616 AC: 180 AN: 292

European-Non Finnish (NFE) AF: 0.505 AC: 34159 AN: 67660

Other (OTH) AF: 0.527 AC: 1101 AN: 2090

Alfa AF: 0.462 Hom.: 8219

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
PhyloP100		0.040

Splicing

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

Other links and lift over

dbSNP: rs9272143; hg19: chr6-32600803;