6-32652845-A-T

Variant names:

• chr6-32652845-A-T
• rs17612858
• XM_006715079.5:c.614-1822A>T

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.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
• Publications: 13 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

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

African (AFR) AF: 0.504 AC: 20184 AN: 40042

American (AMR) AF: 0.648 AC: 9674 AN: 14936

Ashkenazi Jewish (ASJ) AF: 0.627 AC: 2142 AN: 3416

East Asian (EAS) AF: 0.599 AC: 3013 AN: 5028

South Asian (SAS) AF: 0.499 AC: 2306 AN: 4622

European-Finnish (FIN) AF: 0.499 AC: 5057 AN: 10134

Middle Eastern (MID) AF: 0.699 AC: 204 AN: 292

European-Non Finnish (NFE) AF: 0.584 AC: 39091 AN: 66944

Other (OTH) AF: 0.575 AC: 1170 AN: 2036

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.30
DANN	Benign	0.28
PhyloP100		-1.7

Splicing

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

Other links and lift over

dbSNP: rs17612858; hg19: chr6-32620622;