6-32442010-T-C

Position:

• chr6-32442010-T-C

Variant summary

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

The NM_019111.5(HLA-DRA):​c.83-438T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 151,616 control chromosomes in the GnomAD database, including 18,593 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 (18593 hom., cov: 31)
• Consequence: HLA-DRA NM_019111.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.347

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-DRA	NM_019111.5	c.83-438T>C		intron_variant		ENST00000395388.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-DRA	ENST00000395388.7	c.83-438T>C		intron_variant			NM_019111.5	P1
HLA-DRA	ENST00000374982.5	c.83-438T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73837 AN: 151498 Hom.: 18583 Cov.: 31

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.660

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.666

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.523

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

GnomAD4 genome AF: 0.487 AC: 73883 AN: 151616 Hom.: 18593 Cov.: 31 AF XY: 0.485 AC XY: 35908 AN XY: 74092

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.563

Gnomad4 ASJ AF: 0.684

Gnomad4 EAS AF: 0.660

Gnomad4 SAS AF: 0.600

Gnomad4 FIN AF: 0.293

Gnomad4 NFE AF: 0.455

Gnomad4 OTH AF: 0.527

Alfa AF: 0.484 Hom.: 8048

Bravo AF: 0.511

Asia WGS AF: 0.596 AC: 2070 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.9
DANN	Benign	0.62

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: rs6911419; hg19: chr6-32409787;