rs17843604

Positions:

• chr6-32652506-C-T

Variant summary

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

The XM_006715079.5(HLA-DQA1):​c.614-2161C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 147,426 control chromosomes in the GnomAD database, including 18,842 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 0.50 (18842 hom., cov: 26)
• Consequence: HLA-DQA1 XM_006715079.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.860

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DQA1	XM_006715079.5	c.614-2161C>T		intron_variant			XP_006715142.1
		n.32652506C>T		intergenic_region

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.496 AC: 73082 AN: 147314 Hom.: 18841 Cov.: 26

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.681

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.525

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

GnomAD4 genome AF: 0.496 AC: 73126 AN: 147426 Hom.: 18842 Cov.: 26 AF XY: 0.488 AC XY: 35008 AN XY: 71810

Gnomad4 AFR AF: 0.401

Gnomad4 AMR AF: 0.557

Gnomad4 ASJ AF: 0.616

Gnomad4 EAS AF: 0.494

Gnomad4 SAS AF: 0.447

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.551

Gnomad4 OTH AF: 0.521

Alfa AF: 0.563 Hom.: 25192

Bravo AF: 0.517

Asia WGS AF: 0.401 AC: 1396 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.23
DANN	Benign	0.25

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17843604; hg19: chr6-32620283; COSMIC: COSV68419671;