6-32652845-A-T

Position:

• chr6-32652845-A-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.614-1822A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 148,350 control chromosomes in the GnomAD database, including 24,358 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 0.56 (24358 hom., cov: 27)
• Consequence: HLA-DQA1 XM_006715079.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DQA1	XM_006715079.5	c.614-1822A>T		intron_variant			XP_006715142.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.562 AC: 83316 AN: 148226 Hom.: 24349 Cov.: 27

Gnomad AFR AF: 0.504

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.500

Gnomad FIN AF: 0.499

Gnomad MID AF: 0.705

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.579

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

GnomAD4 genome AF: 0.562 AC: 83374 AN: 148350 Hom.: 24358 Cov.: 27 AF XY: 0.558 AC XY: 40344 AN XY: 72266

Gnomad4 AFR AF: 0.504

Gnomad4 AMR AF: 0.648

Gnomad4 ASJ AF: 0.627

Gnomad4 EAS AF: 0.599

Gnomad4 SAS AF: 0.499

Gnomad4 FIN AF: 0.499

Gnomad4 NFE AF: 0.584

Gnomad4 OTH AF: 0.575

Alfa AF: 0.578 Hom.: 3040

Bravo AF: 0.584

Asia WGS AF: 0.485 AC: 1684 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.30
DANN	Benign	0.28

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17612858; hg19: chr6-32620622;