6-32637494-C-T

Variant names:

• chr6-32637494-C-T
• rs1047993
• NM_002122.5:c.36C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002122.5(HLA-DQA1):​c.36C>T​(p.Leu12Leu) 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
• Publications: 25 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]

HLA-DQA1-AS1 (HGNC:56667): (HLA-DQA1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002122.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DQA1	NM_002122.5	MANE Select	c.36C>T	p.Leu12Leu	synonymous	Exon 1 of 5	NP_002113.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DQA1	ENST00000343139.11	TSL:6 MANE Select	c.36C>T	p.Leu12Leu	synonymous	Exon 1 of 5	ENSP00000339398.5
	HLA-DQA1	ENST00000374949.2	TSL:6	c.36C>T	p.Leu12Leu	synonymous	Exon 1 of 4	ENSP00000364087.2
	HLA-DQA1	ENST00000395363.5	TSL:6	c.36C>T	p.Leu12Leu	synonymous	Exon 1 of 5	ENSP00000378767.1

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

GnomAD2 exomes AF: 0.209 AC: 44853 AN: 215000 AF XY: 0.206

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 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

African (AFR) AF: 0.154 AC: 4122 AN: 26830

American (AMR) AF: 0.297 AC: 9390 AN: 31594

Ashkenazi Jewish (ASJ) AF: 0.0717 AC: 1279 AN: 17848

East Asian (EAS) AF: 0.108 AC: 3068 AN: 28464

South Asian (SAS) AF: 0.0770 AC: 5155 AN: 66972

European-Finnish (FIN) AF: 0.141 AC: 6171 AN: 43670

Middle Eastern (MID) AF: 0.0480 AC: 164 AN: 3416

European-Non Finnish (NFE) AF: 0.0500 AC: 37946 AN: 759240

Other (OTH) AF: 0.0740 AC: 3173 AN: 42854

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0675 AC: 1778 AN: 26336

American (AMR) AF: 0.0512 AC: 387 AN: 7562

Ashkenazi Jewish (ASJ) AF: 0.00831 AC: 16 AN: 1926

East Asian (EAS) AF: 0.0669 AC: 191 AN: 2856

South Asian (SAS) AF: 0.0300 AC: 90 AN: 3004

European-Finnish (FIN) AF: 0.0691 AC: 458 AN: 6630

Middle Eastern (MID) AF: 0.0147 AC: 2 AN: 136

European-Non Finnish (NFE) AF: 0.0228 AC: 948 AN: 41634

Other (OTH) AF: 0.0413 AC: 51 AN: 1234

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.166 Hom.: 672

Asia WGS AF: 0.253 AC: 878 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.6
DANN	Benign	0.53
PhyloP100		-2.2
PromoterAI		-0.094	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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