chr6-32634492-G-T

Position:

• chr6-32634492-G-T

Variant summary

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

The ENST00000422863.1(HLA-DQA1):​c.-39+1583G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 151,384 control chromosomes in the GnomAD database, including 6,814 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 0.29 (6814 hom., cov: 30)
• Consequence: HLA-DQA1 ENST00000422863.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.32634492G>T		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DQA1	ENST00000422863.1	c.-39+1583G>T		intron_variant		6		ENSP00000405797.1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44013 AN: 151270 Hom.: 6813 Cov.: 30

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.291 AC: 44035 AN: 151384 Hom.: 6814 Cov.: 30 AF XY: 0.290 AC XY: 21478 AN XY: 73998

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.296

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.306

Alfa AF: 0.293 Hom.: 7127

Bravo AF: 0.297

Asia WGS AF: 0.253 AC: 877 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.16
DANN	Benign	0.21

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9272219; hg19: chr6-32602269;