chr6-32442939-G-A

Position:

• chr6-32442939-G-A

Variant summary

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

The NM_019111.5(HLA-DRA):​c.328+246G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 151,902 control chromosomes in the GnomAD database, including 18,797 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 0.49 (18797 hom., cov: 31)
• Consequence: HLA-DRA NM_019111.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.216

Genes affected

HLA-DRA (HGNC:4947): (major histocompatibility complex, class II, DR alpha) HLA-DRA is one of the HLA class II alpha chain paralogues. This class II molecule is a heterodimer consisting of an alpha and a beta chain, both anchored in the membrane. This molecule is expressed on the surface of various antigen presenting cells such as B lymphocytes, dendritic cells, and monocytes/macrophages, and plays a central role in the immune system and response by presenting peptides derived from extracellular proteins, in particular, pathogen-derived peptides to T cells. The alpha chain is approximately 33-35 kDa and its gene contains 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. DRA does not have polymorphisms in the peptide binding part and acts as the sole alpha chain for DRB1, DRB3, DRB4 and DRB5. [provided by RefSeq, Aug 2020]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DRA	NM_019111.5	c.328+246G>A		intron_variant		ENST00000395388.7	NP_061984.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DRA	ENST00000395388.7	c.328+246G>A		intron_variant			NM_019111.5	ENSP00000378786	P1
HLA-DRA	ENST00000374982.5	c.328+246G>A		intron_variant				ENSP00000364121

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74199 AN: 151784 Hom.: 18787 Cov.: 31

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.664

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.489 AC: 74245 AN: 151902 Hom.: 18797 Cov.: 31 AF XY: 0.486 AC XY: 36107 AN XY: 74220

Gnomad4 AFR AF: 0.512

Gnomad4 AMR AF: 0.563

Gnomad4 ASJ AF: 0.685

Gnomad4 EAS AF: 0.664

Gnomad4 SAS AF: 0.601

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.456

Gnomad4 OTH AF: 0.528

Alfa AF: 0.482 Hom.: 16088

Bravo AF: 0.511

Asia WGS AF: 0.597 AC: 2073 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	14
DANN	Benign	0.71

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: rs9268658; hg19: chr6-32410716; COSMIC: COSV66622827;