6-32637494-C-T

Position:

• chr6-32637494-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002122.5(HLA-DQA1):​c.36C>T​(p.Leu12=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0669 in 1,112,814 control chromosomes in the GnomAD database, including 17,023 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 0.043 (368 hom., cov: 15)
  • Exomes 𝑓: 0.069 (16655 hom.)
• Consequence: HLA-DQA1 NM_002122.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.18

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]

HLA-DQA1-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=-2.18 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DQA1	NM_002122.5	c.36C>T	p.Leu12=	synonymous_variant	1/5	ENST00000343139.11	NP_002113.2
HLA-DQA1-AS1	XR_007059544.1	n.2669G>A		non_coding_transcript_exon_variant	2/2
HLA-DQA1	XM_006715079.5	c.36C>T	p.Leu12=	synonymous_variant	1/4		XP_006715142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DQA1	ENST00000343139.11	c.36C>T	p.Leu12=	synonymous_variant	1/5		NM_002122.5	ENSP00000339398	P1

Frequencies

GnomAD3 genomes AF: 0.0428 AC: 3928 AN: 91832 Hom.: 370 Cov.: 15

Gnomad AFR AF: 0.0677

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0512

Gnomad ASJ AF: 0.00831

Gnomad EAS AF: 0.0669

Gnomad SAS AF: 0.0300

Gnomad FIN AF: 0.0691

Gnomad MID AF: 0.0141

Gnomad NFE AF: 0.0228

Gnomad OTH AF: 0.0419

GnomAD3 exomes AF: 0.209 AC: 44853 AN: 215000 Hom.: 8485 AF XY: 0.206 AC XY: 23813 AN XY: 115568

Gnomad AFR exome AF: 0.195

Gnomad AMR exome AF: 0.311

Gnomad ASJ exome AF: 0.207

Gnomad EAS exome AF: 0.170

Gnomad SAS exome AF: 0.192

Gnomad FIN exome AF: 0.225

Gnomad NFE exome AF: 0.189

Gnomad OTH exome AF: 0.171

GnomAD4 exome AF: 0.0690 AC: 70468 AN: 1020888 Hom.: 16655 Cov.: 26 AF XY: 0.0699 AC XY: 35825 AN XY: 512356

Gnomad4 AFR exome AF: 0.154

Gnomad4 AMR exome AF: 0.297

Gnomad4 ASJ exome AF: 0.0717

Gnomad4 EAS exome AF: 0.108

Gnomad4 SAS exome AF: 0.0770

Gnomad4 FIN exome AF: 0.141

Gnomad4 NFE exome AF: 0.0500

Gnomad4 OTH exome AF: 0.0740

GnomAD4 genome AF: 0.0427 AC: 3927 AN: 91926 Hom.: 368 Cov.: 15 AF XY: 0.0462 AC XY: 2067 AN XY: 44704

Gnomad4 AFR AF: 0.0675

Gnomad4 AMR AF: 0.0512

Gnomad4 ASJ AF: 0.00831

Gnomad4 EAS AF: 0.0669

Gnomad4 SAS AF: 0.0300

Gnomad4 FIN AF: 0.0691

Gnomad4 NFE AF: 0.0228

Gnomad4 OTH AF: 0.0413

Alfa AF: 0.166 Hom.: 672

Asia WGS AF: 0.253 AC: 878 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.6
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1047993; hg19: chr6-32605271; COSMIC: COSV58241054;