rs9272535

Variant names:

• chr6-32638979-G-A
• rs9272535
• NM_002122.5:c.82+1439G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_002122.5(HLA-DQA1):​c.82+1439G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0017 (2 hom., cov: 18)
  • Exomes 𝑓: 0.0033 (94 hom.)
• Consequence: HLA-DQA1 NM_002122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.236
• Publications: 55 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DQA1	NM_002122.5	c.82+1439G>A		intron_variant	Intron 1 of 4	ENST00000343139.11	NP_002113.2
HLA-DQA1-AS1	XR_007059544.1	n.1184C>T		non_coding_transcript_exon_variant	Exon 2 of 2
HLA-DQA1	XM_006715079.5	c.82+1439G>A		intron_variant	Intron 1 of 3		XP_006715142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DQA1	ENST00000343139.11	c.82+1439G>A		intron_variant	Intron 1 of 4	6	NM_002122.5	ENSP00000339398.5

Frequencies

GnomAD3 genomes AF: 0.00166 AC: 192 AN: 115648 Hom.: 2 Cov.: 18

Gnomad AFR AF: 0.00235

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00195

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00285

Gnomad SAS AF: 0.00258

Gnomad FIN AF: 0.00360

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000847

Gnomad OTH AF: 0.00199

GnomAD2 exomes AF: 0.0000299 AC: 3 AN: 100358 AF XY: 0.0000360

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000784

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00328 AC: 756 AN: 230626 Hom.: 94 Cov.: 0 AF XY: 0.00360 AC XY: 477 AN XY: 132640

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

African (AFR) AF: 0.00497 AC: 32 AN: 6436

American (AMR) AF: 0.00723 AC: 137 AN: 18948

Ashkenazi Jewish (ASJ) AF: 0.000732 AC: 6 AN: 8202

East Asian (EAS) AF: 0.00353 AC: 25 AN: 7088

South Asian (SAS) AF: 0.000960 AC: 43 AN: 44802

European-Finnish (FIN) AF: 0.00518 AC: 51 AN: 9848

Middle Eastern (MID) AF: 0.00197 AC: 4 AN: 2026

European-Non Finnish (NFE) AF: 0.00328 AC: 401 AN: 122384

Other (OTH) AF: 0.00523 AC: 57 AN: 10892

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00166 AC: 192 AN: 115760 Hom.: 2 Cov.: 18 AF XY: 0.00174 AC XY: 98 AN XY: 56346

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

African (AFR) AF: 0.00234 AC: 72 AN: 30704

American (AMR) AF: 0.00195 AC: 21 AN: 10792

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2692

East Asian (EAS) AF: 0.00286 AC: 12 AN: 4202

South Asian (SAS) AF: 0.00257 AC: 9 AN: 3498

European-Finnish (FIN) AF: 0.00360 AC: 30 AN: 8322

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 172

European-Non Finnish (NFE) AF: 0.000847 AC: 45 AN: 53118

Other (OTH) AF: 0.00196 AC: 3 AN: 1530

⚠️ 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: 0.210 Hom.: 771

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.9
DANN	Benign	0.86
PhyloP100		-0.24
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: rs9272535; hg19: chr6-32606756; COSMIC: COSV104421202; COSMIC: COSV104421202;