6-32440129-T-C

Variant names:

• chr6-32440129-T-C
• rs41270488
• NM_019111.5:c.82+97T>C

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.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
• Publications: 5 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 (NFE) allele frequency at 95% confidence interval = 0.0902 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DRA	NM_019111.5	c.82+97T>C		intron_variant	Intron 1 of 4	ENST00000395388.7	NP_061984.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DRA	ENST00000395388.7	c.82+97T>C		intron_variant	Intron 1 of 4	6	NM_019111.5	ENSP00000378786.2
HLA-DRA	ENST00000374982.5	c.82+97T>C		intron_variant	Intron 1 of 4	6		ENSP00000364121.5
ENSG00000299747	ENST00000766007.1	n.163-1869A>G		intron_variant	Intron 1 of 2

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

African (AFR) AF: 0.0111 AC: 251 AN: 22604

American (AMR) AF: 0.0529 AC: 2156 AN: 40732

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 3229 AN: 22368

East Asian (EAS) AF: 0.00114 AC: 42 AN: 36758

South Asian (SAS) AF: 0.0576 AC: 4227 AN: 73350

European-Finnish (FIN) AF: 0.0426 AC: 2189 AN: 51358

Middle Eastern (MID) AF: 0.135 AC: 633 AN: 4674

European-Non Finnish (NFE) AF: 0.0853 AC: 51383 AN: 602690

Other (OTH) AF: 0.0761 AC: 3186 AN: 41872

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

African (AFR) AF: 0.0129 AC: 534 AN: 41524

American (AMR) AF: 0.0742 AC: 1134 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 460 AN: 3472

East Asian (EAS) AF: 0.00290 AC: 15 AN: 5180

South Asian (SAS) AF: 0.0431 AC: 208 AN: 4822

European-Finnish (FIN) AF: 0.0397 AC: 420 AN: 10590

Middle Eastern (MID) AF: 0.147 AC: 43 AN: 292

European-Non Finnish (NFE) AF: 0.0921 AC: 6265 AN: 67988

Other (OTH) AF: 0.0665 AC: 140 AN: 2106

Alfa AF: 0.0770 Hom.: 398

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
PhyloP100		2.0
PromoterAI		0.066	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs41270488; hg19: chr6-32407906;