chr6-32638944-G-T

Variant names:

• chr6-32638944-G-T
• rs75983419
• NM_002122.5:c.82+1404G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002122.5(HLA-DQA1):​c.82+1404G>T 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 0.091 (2444 hom., cov: 18)
  • Exomes 𝑓: 0.076 (3754 hom.)
• Consequence: HLA-DQA1 NM_002122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DQA1	NM_002122.5	c.82+1404G>T		intron_variant	Intron 1 of 4	ENST00000343139.11	NP_002113.2
HLA-DQA1-AS1	XR_007059544.1	n.1219C>A		non_coding_transcript_exon_variant	Exon 2 of 2
HLA-DQA1	XM_006715079.5	c.82+1404G>T		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+1404G>T		intron_variant	Intron 1 of 4	6	NM_002122.5	ENSP00000339398.5

Frequencies

GnomAD3 genomes AF: 0.0911 AC: 10270 AN: 112674 Hom.: 2442 Cov.: 18

Gnomad AFR AF: 0.0660

Gnomad AMI AF: 0.0332

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.00943

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.0769

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.105

GnomAD2 exomes AF: 0.0585 AC: 5529 AN: 94508 AF XY: 0.0636

Gnomad AFR exome AF: 0.0263

Gnomad AMR exome AF: 0.0359

Gnomad ASJ exome AF: 0.0942

Gnomad EAS exome AF: 0.00460

Gnomad FIN exome AF: 0.0915

Gnomad NFE exome AF: 0.0617

Gnomad OTH exome AF: 0.0549

GnomAD4 exome AF: 0.0763 AC: 17742 AN: 232676 Hom.: 3754 Cov.: 0 AF XY: 0.0792 AC XY: 10584 AN XY: 133562

African (AFR) AF: 0.0439 AC: 282 AN: 6430

American (AMR) AF: 0.0476 AC: 910 AN: 19110

Ashkenazi Jewish (ASJ) AF: 0.0963 AC: 798 AN: 8284

East Asian (EAS) AF: 0.00754 AC: 55 AN: 7296

South Asian (SAS) AF: 0.0931 AC: 4205 AN: 45182

European-Finnish (FIN) AF: 0.110 AC: 1075 AN: 9740

Middle Eastern (MID) AF: 0.0556 AC: 112 AN: 2014

European-Non Finnish (NFE) AF: 0.0767 AC: 9485 AN: 123652

Other (OTH) AF: 0.0748 AC: 820 AN: 10968

GnomAD4 genome AF: 0.0911 AC: 10275 AN: 112792 Hom.: 2444 Cov.: 18 AF XY: 0.0924 AC XY: 5071 AN XY: 54852

African (AFR) AF: 0.0661 AC: 1986 AN: 30028

American (AMR) AF: 0.112 AC: 1168 AN: 10400

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 341 AN: 2634

East Asian (EAS) AF: 0.00969 AC: 40 AN: 4126

South Asian (SAS) AF: 0.101 AC: 342 AN: 3382

European-Finnish (FIN) AF: 0.122 AC: 977 AN: 8016

Middle Eastern (MID) AF: 0.0698 AC: 12 AN: 172

European-Non Finnish (NFE) AF: 0.101 AC: 5230 AN: 51806

Other (OTH) AF: 0.103 AC: 155 AN: 1506

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.53
DANN	Benign	0.36
PhyloP100		-2.0
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: rs75983419; hg19: chr6-32606721;