chr6-32440129-T-C

Position:

• chr6-32440129-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.82+97T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0731 in 1,048,576 control chromosomes in the GnomAD database, including 3,924 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 0.061 (478 hom., cov: 30)
  • Exomes 𝑓: 0.075 (3446 hom.)
• Consequence: HLA-DRA NM_019111.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.97

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 (NFE) allele frequency at 95% confidence interval = 0.0902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-DRA	NM_019111.5	c.82+97T>C		intron_variant		ENST00000395388.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-DRA	ENST00000395388.7	c.82+97T>C		intron_variant			NM_019111.5	P1
HLA-DRA	ENST00000374982.5	c.82+97T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0613 AC: 9322 AN: 152052 Hom.: 478 Cov.: 30

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.108

Gnomad AMR AF: 0.0743

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.0433

Gnomad FIN AF: 0.0397

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.0921

Gnomad OTH AF: 0.0672

GnomAD4 exome AF: 0.0751 AC: 67296 AN: 896406 Hom.: 3446 AF XY: 0.0769 AC XY: 35731 AN XY: 464648

Gnomad4 AFR exome AF: 0.0111

Gnomad4 AMR exome AF: 0.0529

Gnomad4 ASJ exome AF: 0.144

Gnomad4 EAS exome AF: 0.00114

Gnomad4 SAS exome AF: 0.0576

Gnomad4 FIN exome AF: 0.0426

Gnomad4 NFE exome AF: 0.0853

Gnomad4 OTH exome AF: 0.0761

GnomAD4 genome AF: 0.0612 AC: 9317 AN: 152170 Hom.: 478 Cov.: 30 AF XY: 0.0590 AC XY: 4393 AN XY: 74396

Gnomad4 AFR AF: 0.0129

Gnomad4 AMR AF: 0.0742

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.00290

Gnomad4 SAS AF: 0.0431

Gnomad4 FIN AF: 0.0397

Gnomad4 NFE AF: 0.0921

Gnomad4 OTH AF: 0.0665

Alfa AF: 0.0858 Hom.: 162

Bravo AF: 0.0604

Asia WGS AF: 0.0180 AC: 63 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	11
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs41270488; hg19: chr6-32407906;