XM_006715079.5:c.613+5680G>C

Variant names:

• chr6-32647933-G-C
• rs17612633
• XM_006715079.5:c.613+5680G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_006715079.5(HLA-DQA1):​c.613+5680G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.568 in 150,236 control chromosomes in the GnomAD database, including 24,694 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 0.57 (24694 hom., cov: 30)
• Consequence: HLA-DQA1 XM_006715079.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 14 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DQA1	XM_006715079.5	c.613+5680G>C		intron_variant	Intron 3 of 3		XP_006715142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.568 AC: 85334 AN: 150114 Hom.: 24685 Cov.: 30

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.596

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.607

Gnomad SAS AF: 0.509

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.714

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.586

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

GnomAD4 genome AF: 0.568 AC: 85392 AN: 150236 Hom.: 24694 Cov.: 30 AF XY: 0.565 AC XY: 41447 AN XY: 73320

African (AFR) AF: 0.516 AC: 21119 AN: 40900

American (AMR) AF: 0.653 AC: 9862 AN: 15112

Ashkenazi Jewish (ASJ) AF: 0.628 AC: 2155 AN: 3434

East Asian (EAS) AF: 0.608 AC: 3112 AN: 5122

South Asian (SAS) AF: 0.508 AC: 2406 AN: 4734

European-Finnish (FIN) AF: 0.515 AC: 5322 AN: 10328

Middle Eastern (MID) AF: 0.705 AC: 203 AN: 288

European-Non Finnish (NFE) AF: 0.586 AC: 39469 AN: 67342

Other (OTH) AF: 0.582 AC: 1210 AN: 2080

Alfa AF: 0.448 Hom.: 1158

Bravo AF: 0.584

Asia WGS AF: 0.486 AC: 1689 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	0.30
DANN	Benign	0.27
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs17612633; hg19: chr6-32615710;