NM_019111.5:c.82+718C>G

Variant names:

• chr6-32440750-C-G
• rs9268645
• NM_019111.5:c.82+718C>G

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+718C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 152,078 control chromosomes in the GnomAD database, including 11,707 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 0.39 (11707 hom., cov: 32)
• Consequence: HLA-DRA NM_019111.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.156
• Publications: 86 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.536 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DRA	NM_019111.5	MANE Select	c.82+718C>G		intron	N/A	NP_061984.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DRA	ENST00000395388.7	TSL:6 MANE Select	c.82+718C>G		intron	N/A	ENSP00000378786.2
	HLA-DRA	ENST00000374982.5	TSL:6	c.82+718C>G		intron	N/A	ENSP00000364121.5
	ENSG00000299747	ENST00000766007.1		n.163-2490G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58808 AN: 151960 Hom.: 11706 Cov.: 32

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.408

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

GnomAD4 genome AF: 0.387 AC: 58829 AN: 152078 Hom.: 11707 Cov.: 32 AF XY: 0.389 AC XY: 28923 AN XY: 74338

African (AFR) AF: 0.342 AC: 14182 AN: 41500

American (AMR) AF: 0.451 AC: 6891 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 1794 AN: 3472

East Asian (EAS) AF: 0.553 AC: 2858 AN: 5170

South Asian (SAS) AF: 0.511 AC: 2458 AN: 4808

European-Finnish (FIN) AF: 0.292 AC: 3086 AN: 10572

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.385 AC: 26190 AN: 67956

Other (OTH) AF: 0.411 AC: 869 AN: 2114

Alfa AF: 0.393 Hom.: 6746

Bravo AF: 0.396

Asia WGS AF: 0.470 AC: 1634 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.5
DANN	Benign	0.37
PhyloP100		0.16
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: rs9268645; hg19: chr6-32408527; COSMIC: COSV66622973;