rs1129740

Positions:

• chr6-32641328-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002122.5(HLA-DQA1):​c.101G>A​(p.Cys34Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.26 (4413 hom., cov: 16)
  • Exomes 𝑓: 0.29 (93358 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-DQA1 NM_002122.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.525

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:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.0995187E-5).
• BP6: Variant 6-32641328-G-A is Benign according to our data. Variant chr6-32641328-G-A is described in ClinVar as [Benign]. Clinvar id is 1258533.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DQA1	NM_002122.5	c.101G>A	p.Cys34Tyr	missense_variant	2/5	ENST00000343139.11	NP_002113.2
HLA-DQA1	XM_006715079.5	c.101G>A	p.Cys34Tyr	missense_variant	2/4		XP_006715142.1
HLA-DQA1-AS1	XR_007059544.1			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DQA1	ENST00000343139.11	c.101G>A	p.Cys34Tyr	missense_variant	2/5		NM_002122.5	ENSP00000339398	P1

Frequencies

GnomAD3 genomes AF: 0.256 AC: 20344 AN: 79544 Hom.: 4407 Cov.: 16

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.256

GnomAD3 exomes AF: 0.495 AC: 94628 AN: 191328 Hom.: 36252 AF XY: 0.496 AC XY: 51363 AN XY: 103594

Gnomad AFR exome AF: 0.417

Gnomad AMR exome AF: 0.662

Gnomad ASJ exome AF: 0.556

Gnomad EAS exome AF: 0.450

Gnomad SAS exome AF: 0.434

Gnomad FIN exome AF: 0.403

Gnomad NFE exome AF: 0.496

Gnomad OTH exome AF: 0.458

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.292 AC: 266227 AN: 910226 Hom.: 93358 Cov.: 27 AF XY: 0.303 AC XY: 139266 AN XY: 460174

Gnomad4 AFR exome AF: 0.220

Gnomad4 AMR exome AF: 0.549

Gnomad4 ASJ exome AF: 0.362

Gnomad4 EAS exome AF: 0.140

Gnomad4 SAS exome AF: 0.386

Gnomad4 FIN exome AF: 0.212

Gnomad4 NFE exome AF: 0.285

Gnomad4 OTH exome AF: 0.259

GnomAD4 genome AF: 0.256 AC: 20360 AN: 79622 Hom.: 4413 Cov.: 16 AF XY: 0.251 AC XY: 9728 AN XY: 38744

Gnomad4 AFR AF: 0.214

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.321

Gnomad4 EAS AF: 0.187

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.305

Gnomad4 OTH AF: 0.252

Alfa AF: 0.589 Hom.: 32572

ESP6500AA AF: 0.424 AC: 1866

ESP6500EA AF: 0.465 AC: 3996

ExAC AF: 0.556 AC: 67297

Asia WGS AF: 0.469 AC: 1584 AN: 3374

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 15, 2020

This variant is associated with the following publications: (PMID: 25349203) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.075
DANN	Benign	0.23
DEOGEN2	Benign	0.0012	.;.;T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0020	N
LIST_S2	Benign	0.70	.;.;T;T
MetaRNN	Benign	0.000021	T;T;T;T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	1.0	P;P;P;P
PrimateAI	Benign	0.39	T
PROVEAN	Benign	4.8	N;N;N;N
REVEL	Benign	0.28
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Vest4		0.060
MPC		1.4
ClinPred		0.0047	T
GERP RS		-0.28
gMVP		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1129740; hg19: chr6-32609105; COSMIC: COSV58237735; COSMIC: COSV58237735;