ENST00000422863.1:c.-39+1796T>C

Variant names:

• chr6-32634705-T-C
• rs3104369
• ENST00000422863.1:c.-39+1796T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000422863.1(HLA-DQA1):​c.-39+1796T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 151,256 control chromosomes in the GnomAD database, including 38,203 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 0.71 (38203 hom., cov: 30)
• Consequence: HLA-DQA1 ENST00000422863.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.385

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.743 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+1796T>C		intron_variant	Intron 3 of 3	6		ENSP00000405797.1

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107127 AN: 151138 Hom.: 38178 Cov.: 30

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.880

Gnomad AMR AF: 0.746

Gnomad ASJ AF: 0.832

Gnomad EAS AF: 0.706

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.812

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.749

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

GnomAD4 genome AF: 0.709 AC: 107213 AN: 151256 Hom.: 38203 Cov.: 30 AF XY: 0.703 AC XY: 51974 AN XY: 73912

Gnomad4 AFR AF: 0.631

Gnomad4 AMR AF: 0.746

Gnomad4 ASJ AF: 0.832

Gnomad4 EAS AF: 0.706

Gnomad4 SAS AF: 0.653

Gnomad4 FIN AF: 0.666

Gnomad4 NFE AF: 0.749

Gnomad4 OTH AF: 0.745

Alfa AF: 0.743 Hom.: 61838

Bravo AF: 0.713

Asia WGS AF: 0.618 AC: 2153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	6.6
DANN	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3104369; hg19: chr6-32602482;