6-32641349-T-C

Position:

• chr6-32641349-T-C

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.122T>C​(p.Phe41Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (3842 hom., cov: 15)
  • Exomes 𝑓: 0.23 (68797 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-DQA1 NM_002122.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.905

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.1289733E-5).
• BP6: Variant 6-32641349-T-C is Benign according to our data. Variant chr6-32641349-T-C is described in ClinVar as [Benign]. Clinvar id is 1257290.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DQA1	NM_002122.5	c.122T>C	p.Phe41Ser	missense_variant	2/5	ENST00000343139.11	NP_002113.2
HLA-DQA1	XM_006715079.5	c.122T>C	p.Phe41Ser	missense_variant	2/4		XP_006715142.1
HLA-DQA1-AS1	XR_007059544.1	n.-39A>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DQA1	ENST00000343139.11	c.122T>C	p.Phe41Ser	missense_variant	2/5	6	NM_002122.5	ENSP00000339398.5

Frequencies

GnomAD3 genomes AF: 0.228 AC: 18563 AN: 81386 Hom.: 3838 Cov.: 15

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.276

Gnomad OTH AF: 0.240

GnomAD3 exomes AF: 0.493 AC: 92599 AN: 187738 Hom.: 36235 AF XY: 0.494 AC XY: 50112 AN XY: 101454

Gnomad AFR exome AF: 0.415

Gnomad AMR exome AF: 0.668

Gnomad ASJ exome AF: 0.551

Gnomad EAS exome AF: 0.449

Gnomad SAS exome AF: 0.424

Gnomad FIN exome AF: 0.403

Gnomad NFE exome AF: 0.495

Gnomad OTH exome AF: 0.450

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.232 AC: 192749 AN: 831528 Hom.: 68797 Cov.: 25 AF XY: 0.247 AC XY: 104198 AN XY: 422096

Gnomad4 AFR exome AF: 0.178

Gnomad4 AMR exome AF: 0.534

Gnomad4 ASJ exome AF: 0.330

Gnomad4 EAS exome AF: 0.129

Gnomad4 SAS exome AF: 0.358

Gnomad4 FIN exome AF: 0.197

Gnomad4 NFE exome AF: 0.213

Gnomad4 OTH exome AF: 0.204

GnomAD4 genome AF: 0.228 AC: 18572 AN: 81452 Hom.: 3842 Cov.: 15 AF XY: 0.225 AC XY: 8955 AN XY: 39856

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.197

Gnomad4 ASJ AF: 0.292

Gnomad4 EAS AF: 0.146

Gnomad4 SAS AF: 0.202

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.276

Gnomad4 OTH AF: 0.235

Alfa AF: 0.581 Hom.: 21374

ESP6500AA AF: 0.388 AC: 1711

ESP6500EA AF: 0.441 AC: 3781

ExAC AF: 0.555 AC: 67214

Asia WGS AF: 0.469 AC: 1583 AN: 3376

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	-0.52	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	5.3
DANN	Benign	0.15
DEOGEN2	Benign	0.0032	.;.;T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0013	N
LIST_S2	Benign	0.34	.;.;T;T
MetaRNN	Benign	0.000011	T;T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.41	T
PROVEAN	Benign	3.1	N;N;N;N
REVEL	Uncertain	0.29
Sift	Benign	1.0	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Vest4		0.040
MPC		1.4
ClinPred		0.000028	T
GERP RS		3.0
gMVP		0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs1071630; hg19: chr6-32609126; COSMIC: COSV58239937; COSMIC: COSV58239937;