ENST00000422863.1:c.-39+1528G>A

Variant names:

• chr6-32634437-G-A
• rs4639334
• ENST00000422863.1:c.-39+1528G>A

Variant summary

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

The ENST00000422863.1(HLA-DQA1):​c.-39+1528G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 151,546 control chromosomes in the GnomAD database, including 1,405 homozygotes. 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 0.12 (1405 hom., cov: 29)
• Consequence: HLA-DQA1 ENST00000422863.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0240
• Publications: 24 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DQA1	ENST00000422863.1	c.-39+1528G>A		intron_variant	Intron 3 of 3	6		ENSP00000405797.1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18769 AN: 151434 Hom.: 1403 Cov.: 29

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.0863

Gnomad SAS AF: 0.0832

Gnomad FIN AF: 0.0714

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.124 AC: 18784 AN: 151546 Hom.: 1405 Cov.: 29 AF XY: 0.121 AC XY: 8957 AN XY: 74064

African (AFR) AF: 0.129 AC: 5320 AN: 41232

American (AMR) AF: 0.133 AC: 2020 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 765 AN: 3462

East Asian (EAS) AF: 0.0863 AC: 445 AN: 5156

South Asian (SAS) AF: 0.0828 AC: 398 AN: 4806

European-Finnish (FIN) AF: 0.0714 AC: 750 AN: 10500

Middle Eastern (MID) AF: 0.299 AC: 86 AN: 288

European-Non Finnish (NFE) AF: 0.126 AC: 8573 AN: 67884

Other (OTH) AF: 0.156 AC: 327 AN: 2094

Alfa AF: 0.125 Hom.: 139

Bravo AF: 0.130

Asia WGS AF: 0.101 AC: 351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.2
DANN	Benign	0.48
PhyloP100		-0.024

Splicing

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

Other links and lift over

dbSNP: rs4639334; hg19: chr6-32602214;