rs9272218

Positions:

• chr6-32634461-C-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+1552C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 151,206 control chromosomes in the GnomAD database, including 23,260 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 0.55 (23260 hom., cov: 29)
• Consequence: HLA-DQA1 ENST00000422863.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.471

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 (AFR) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-DQA1	ENST00000422863.1	c.-39+1552C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83369 AN: 151088 Hom.: 23239 Cov.: 29

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.590

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

GnomAD4 genome AF: 0.552 AC: 83433 AN: 151206 Hom.: 23260 Cov.: 29 AF XY: 0.554 AC XY: 40890 AN XY: 73844

Gnomad4 AFR AF: 0.570

Gnomad4 AMR AF: 0.565

Gnomad4 ASJ AF: 0.585

Gnomad4 EAS AF: 0.464

Gnomad4 SAS AF: 0.506

Gnomad4 FIN AF: 0.616

Gnomad4 NFE AF: 0.536

Gnomad4 OTH AF: 0.587

Alfa AF: 0.533 Hom.: 4135

Bravo AF: 0.547

Asia WGS AF: 0.485 AC: 1687 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.6
DANN	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9272218; hg19: chr6-32602238;