chr6-32442939-G-A

Variant names:

• chr6-32442939-G-A
• rs9268658
• NM_019111.5:c.328+246G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 35 publications found

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]

ENSG00000299747 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_019111.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DRA	NM_019111.5	MANE Select	c.328+246G>A		intron	N/A	NP_061984.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DRA	ENST00000395388.7	TSL:6 MANE Select	c.328+246G>A		intron	N/A	ENSP00000378786.2	P01903
	HLA-DRA	ENST00000870696.1		c.328+246G>A		intron	N/A	ENSP00000540755.1
	HLA-DRA	ENST00000917299.1		c.328+246G>A		intron	N/A	ENSP00000587358.1

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

African (AFR) AF: 0.512 AC: 21173 AN: 41378

American (AMR) AF: 0.563 AC: 8611 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 2379 AN: 3472

East Asian (EAS) AF: 0.664 AC: 3438 AN: 5174

South Asian (SAS) AF: 0.601 AC: 2883 AN: 4796

European-Finnish (FIN) AF: 0.297 AC: 3132 AN: 10546

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.456 AC: 30967 AN: 67942

Other (OTH) AF: 0.528 AC: 1112 AN: 2106

Alfa AF: 0.486 Hom.: 31652

Bravo AF: 0.511

Asia WGS AF: 0.597 AC: 2073 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	14
DANN	Benign	0.71
PhyloP100		0.22
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: rs9268658; hg19: chr6-32410716; COSMIC: COSV66622827;