6-32638985-T-G

Variant names:

• chr6-32638985-T-G
• rs147737004
• NM_002122.5:c.82+1445T>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002122.5(HLA-DQA1):​c.82+1445T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0020 (61 hom., cov: 18)
  • Exomes 𝑓: 0.0048 (308 hom.)
• Consequence: HLA-DQA1 NM_002122.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.750
• Publications: 1 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 6-32638985-T-G is Benign according to our data. Variant chr6-32638985-T-G is described in ClinVar as [Benign]. Clinvar id is 2656470.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 61 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DQA1	NM_002122.5	c.82+1445T>G		intron_variant	Intron 1 of 4	ENST00000343139.11	NP_002113.2
HLA-DQA1-AS1	XR_007059544.1	n.1178A>C		non_coding_transcript_exon_variant	Exon 2 of 2
HLA-DQA1	XM_006715079.5	c.82+1445T>G		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+1445T>G		intron_variant	Intron 1 of 4	6	NM_002122.5	ENSP00000339398.5

Frequencies

GnomAD3 genomes AF: 0.00201 AC: 240 AN: 119660 Hom.: 61 Cov.: 18

Gnomad AFR AF: 0.000281

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00230

Gnomad ASJ AF: 0.00326

Gnomad EAS AF: 0.00182

Gnomad SAS AF: 0.0109

Gnomad FIN AF: 0.000229

Gnomad MID AF: 0.00532

Gnomad NFE AF: 0.00256

Gnomad OTH AF: 0.00453

GnomAD2 exomes AF: 0.00417 AC: 416 AN: 99792 AF XY: 0.00496

Gnomad AFR exome AF: 0.000224

Gnomad AMR exome AF: 0.00242

Gnomad ASJ exome AF: 0.00258

Gnomad EAS exome AF: 0.00176

Gnomad FIN exome AF: 0.000853

Gnomad NFE exome AF: 0.00300

Gnomad OTH exome AF: 0.00321

GnomAD4 exome AF: 0.00476 AC: 1112 AN: 233778 Hom.: 308 Cov.: 0 AF XY: 0.00559 AC XY: 752 AN XY: 134442

African (AFR) AF: 0.000750 AC: 5 AN: 6668

American (AMR) AF: 0.00247 AC: 49 AN: 19844

Ashkenazi Jewish (ASJ) AF: 0.00244 AC: 20 AN: 8186

East Asian (EAS) AF: 0.00232 AC: 17 AN: 7328

South Asian (SAS) AF: 0.0130 AC: 586 AN: 45004

European-Finnish (FIN) AF: 0.000685 AC: 7 AN: 10224

Middle Eastern (MID) AF: 0.00686 AC: 14 AN: 2040

European-Non Finnish (NFE) AF: 0.00300 AC: 370 AN: 123386

Other (OTH) AF: 0.00396 AC: 44 AN: 11098

GnomAD4 genome AF: 0.00200 AC: 240 AN: 119782 Hom.: 61 Cov.: 18 AF XY: 0.00224 AC XY: 131 AN XY: 58404

African (AFR) AF: 0.000280 AC: 9 AN: 32152

American (AMR) AF: 0.00230 AC: 26 AN: 11298

Ashkenazi Jewish (ASJ) AF: 0.00326 AC: 9 AN: 2764

East Asian (EAS) AF: 0.00183 AC: 8 AN: 4382

South Asian (SAS) AF: 0.0109 AC: 39 AN: 3566

European-Finnish (FIN) AF: 0.000229 AC: 2 AN: 8746

Middle Eastern (MID) AF: 0.00568 AC: 1 AN: 176

European-Non Finnish (NFE) AF: 0.00256 AC: 139 AN: 54396

Other (OTH) AF: 0.00448 AC: 7 AN: 1564

Alfa AF: 0.00162 Hom.: 2

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

HLA-DQA1: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.9
DANN	Benign	0.80
PhyloP100		0.75
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs147737004; hg19: chr6-32606762; COSMIC: COSV107445933; COSMIC: COSV107445933;