rs2395228

Variant names:

• chr6-32655446-A-C
• rs2395228
• XM_006715079.5:c.*772A>C

Your query was ambiguous. Multiple possible variants found:

• chr6-32655446-A-C
• chr6-32655446-A-G

Variant summary

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

The XM_006715079.5(HLA-DQA1):​c.*772A>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 124,078 control chromosomes in the GnomAD database, including 846 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 (846 hom., cov: 29)
• Consequence: HLA-DQA1 XM_006715079.5 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.766

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DQA1	XM_006715079.5	c.*772A>C		downstream_gene_variant			XP_006715142.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.116 AC: 14320 AN: 123982 Hom.: 845 Cov.: 29

Gnomad AFR AF: 0.0834

Gnomad AMI AF: 0.0667

Gnomad AMR AF: 0.0837

Gnomad ASJ AF: 0.0762

Gnomad EAS AF: 0.0597

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.0990

Gnomad MID AF: 0.154

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.115 AC: 14327 AN: 124078 Hom.: 846 Cov.: 29 AF XY: 0.113 AC XY: 6811 AN XY: 60454

Gnomad4 AFR AF: 0.0833

Gnomad4 AMR AF: 0.0836

Gnomad4 ASJ AF: 0.0762

Gnomad4 EAS AF: 0.0597

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.0990

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.111

Alfa AF: 0.103 Hom.: 757

Bravo AF: 0.0916

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.1
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2395228; hg19: chr6-32623223;