6-32640300-T-C

Variant names:

• chr6-32640300-T-C
• rs17426593
• NM_002122.5:c.83-1010T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002122.5(HLA-DQA1):​c.83-1010T>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 0.00094 (1 hom., cov: 16)
• Consequence: HLA-DQA1 NM_002122.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.233
• Publications: 19 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DQA1	NM_002122.5	c.83-1010T>C		intron_variant	Intron 1 of 4	ENST00000343139.11	NP_002113.2
HLA-DQA1	XM_006715079.5	c.83-1010T>C		intron_variant	Intron 1 of 3		XP_006715142.1
HLA-DQA1-AS1	XR_007059544.1	n.921+90A>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DQA1	ENST00000343139.11	c.83-1010T>C		intron_variant	Intron 1 of 4	6	NM_002122.5	ENSP00000339398.5

Frequencies

GnomAD3 genomes AF: 0.000929 AC: 87 AN: 93630 Hom.: 1 Cov.: 16

Gnomad AFR AF: 0.000648

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000932

Gnomad ASJ AF: 0.00208

Gnomad EAS AF: 0.00145

Gnomad SAS AF: 0.000635

Gnomad FIN AF: 0.00191

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000885

Gnomad OTH AF: 0.00161

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.000939 AC: 88 AN: 93720 Hom.: 1 Cov.: 16 AF XY: 0.00101 AC XY: 46 AN XY: 45708

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

African (AFR) AF: 0.000646 AC: 18 AN: 27854

American (AMR) AF: 0.000932 AC: 7 AN: 7510

Ashkenazi Jewish (ASJ) AF: 0.00208 AC: 4 AN: 1924

East Asian (EAS) AF: 0.00146 AC: 4 AN: 2742

South Asian (SAS) AF: 0.000951 AC: 3 AN: 3154

European-Finnish (FIN) AF: 0.00191 AC: 13 AN: 6800

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 140

European-Non Finnish (NFE) AF: 0.000885 AC: 37 AN: 41798

Other (OTH) AF: 0.00158 AC: 2 AN: 1264

⚠️ 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: 0.101 Hom.: 192

Asia WGS AF: 0.157 AC: 550 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.3
DANN	Benign	0.43
PhyloP100		0.23
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: rs17426593; hg19: chr6-32608077;