6-32444611-T-A

Position:

• chr6-32444611-T-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.*12-41T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,018 control chromosomes in the GnomAD database, including 1,428 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 0.13 (1428 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-DRA NM_019111.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0970

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=-0.79).
• 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/exons	MANE	UniProt
HLA-DRA	NM_019111.5	c.*12-41T>A		intron_variant		ENST00000395388.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-DRA	ENST00000395388.7	c.*12-41T>A		intron_variant			NM_019111.5	P1
HLA-DRA	ENST00000374982.5	c.*12-41T>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19307 AN: 151900 Hom.: 1428 Cov.: 31

Gnomad AFR AF: 0.0850

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0617

Gnomad EAS AF: 0.0425

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.125

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.127 AC: 19323 AN: 152018 Hom.: 1428 Cov.: 31 AF XY: 0.130 AC XY: 9693 AN XY: 74320

Gnomad4 AFR AF: 0.0851

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.0617

Gnomad4 EAS AF: 0.0424

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.124

Alfa AF: 0.0225 Hom.: 3127

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.6
DANN	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4935356; hg19: chr6-32412388;