rs1047993

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr6-32637494-C-G
• chr6-32637494-C-T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_002122.5(HLA-DQA1):​c.36C>G​(p.Leu12Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000158 in 1,137,092 control chromosomes in the GnomAD database, including 4 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 0.000063 (2 hom., cov: 15)
  • Exomes 𝑓: 0.000012 (2 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP7: Synonymous conserved (PhyloP=-2.18 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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>G	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>G	p.Leu12Leu	synonymous	Exon 1 of 5	ENSP00000339398.5
	HLA-DQA1	ENST00000374949.2	TSL:6	c.36C>G	p.Leu12Leu	synonymous	Exon 1 of 4	ENSP00000364087.2
	HLA-DQA1	ENST00000395363.5	TSL:6	c.36C>G	p.Leu12Leu	synonymous	Exon 1 of 5	ENSP00000378767.1

Frequencies

GnomAD3 genomes AF: 0.0000635 AC: 6 AN: 94514 Hom.: 2 Cov.: 15

Gnomad AFR AF: 0.000182

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000331

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000186 AC: 4 AN: 215000 AF XY: 0.0000173

Gnomad AFR exome AF: 0.0000734

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000192

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000115 AC: 12 AN: 1042486 Hom.: 2 Cov.: 26 AF XY: 0.00000572 AC XY: 3 AN XY: 524084

African (AFR) AF: 0.000180 AC: 5 AN: 27754

American (AMR) AF: 0.00 AC: 0 AN: 32726

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18320

East Asian (EAS) AF: 0.000240 AC: 7 AN: 29182

South Asian (SAS) AF: 0.00 AC: 0 AN: 69796

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44820

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3466

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 772656

Other (OTH) AF: 0.00 AC: 0 AN: 43766

GnomAD4 genome AF: 0.0000634 AC: 6 AN: 94606 Hom.: 2 Cov.: 15 AF XY: 0.000109 AC XY: 5 AN XY: 46064

African (AFR) AF: 0.000182 AC: 5 AN: 27544

American (AMR) AF: 0.00 AC: 0 AN: 7790

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1940

East Asian (EAS) AF: 0.000333 AC: 1 AN: 3004

South Asian (SAS) AF: 0.00 AC: 0 AN: 3068

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6948

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 142

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 42300

Other (OTH) AF: 0.00 AC: 0 AN: 1260

Alfa AF: 0.00 Hom.: 672

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.59
DANN	Benign	0.40
PhyloP100		-2.2
PromoterAI		-0.040	Neutral
Mutation Taster		=100/0	polymorphism

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;