rs9272723

Variant names:

• chr6-32641650-T-C
• rs9272723
• NM_002122.5:c.331+92T>C

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.331+92T>C 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 0.085 (716 hom., cov: 13)
  • Exomes 𝑓: 0.033 (6755 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-DQA1 NM_002122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.987
• Publications: 45 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]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS2: High Homozygotes in GnomAd4 at 716 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DQA1	NM_002122.5	c.331+92T>C		intron_variant	Intron 2 of 4	ENST00000343139.11	NP_002113.2
HLA-DQA1	XM_006715079.5	c.331+92T>C		intron_variant	Intron 2 of 3		XP_006715142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DQA1	ENST00000343139.11	c.331+92T>C		intron_variant	Intron 2 of 4	6	NM_002122.5	ENSP00000339398.5

Frequencies

GnomAD3 genomes AF: 0.0849 AC: 5855 AN: 68982 Hom.: 716 Cov.: 13

Gnomad AFR AF: 0.0706

Gnomad AMI AF: 0.0798

Gnomad AMR AF: 0.0837

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.0662

Gnomad SAS AF: 0.0752

Gnomad FIN AF: 0.0477

Gnomad MID AF: 0.368

Gnomad NFE AF: 0.0994

Gnomad OTH AF: 0.0873

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0326 AC: 16399 AN: 503252 Hom.: 6755 AF XY: 0.0336 AC XY: 8894 AN XY: 264696

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

African (AFR) AF: 0.0320 AC: 490 AN: 15298

American (AMR) AF: 0.0641 AC: 1084 AN: 16912

Ashkenazi Jewish (ASJ) AF: 0.0466 AC: 518 AN: 11108

East Asian (EAS) AF: 0.0200 AC: 446 AN: 22288

South Asian (SAS) AF: 0.0411 AC: 2037 AN: 49580

European-Finnish (FIN) AF: 0.0129 AC: 332 AN: 25644

Middle Eastern (MID) AF: 0.0351 AC: 80 AN: 2280

European-Non Finnish (NFE) AF: 0.0314 AC: 10560 AN: 336394

Other (OTH) AF: 0.0359 AC: 852 AN: 23748

⚠️ 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: 0.0848 AC: 5859 AN: 69052 Hom.: 716 Cov.: 13 AF XY: 0.0820 AC XY: 2754 AN XY: 33590

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

African (AFR) AF: 0.0705 AC: 1386 AN: 19648

American (AMR) AF: 0.0838 AC: 460 AN: 5492

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 167 AN: 1390

East Asian (EAS) AF: 0.0665 AC: 149 AN: 2242

South Asian (SAS) AF: 0.0752 AC: 172 AN: 2286

European-Finnish (FIN) AF: 0.0477 AC: 242 AN: 5074

Middle Eastern (MID) AF: 0.364 AC: 40 AN: 110

European-Non Finnish (NFE) AF: 0.0994 AC: 3130 AN: 31478

Other (OTH) AF: 0.0872 AC: 79 AN: 906

⚠️ 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: 0.549 Hom.: 4344

Asia WGS AF: 0.480 AC: 1656 AN: 3446

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.44
PhyloP100		-0.99
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: rs9272723; hg19: chr6-32609427; COSMIC: COSV58239693; COSMIC: COSV58239693;