rs7195

Variant names:

• chr6-32444762-A-G
• rs7195
• NM_019111.5:c.*122A>G

Variant summary

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

The NM_019111.5(HLA-DRA):​c.*122A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 152,282 control chromosomes in the GnomAD database, including 29,319 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 0.62 (29237 hom., cov: 31)
  • Exomes 𝑓: 0.81 (82 hom.)
• Consequence: HLA-DRA NM_019111.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.204

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 (SAS) allele frequency at 95% confidence interval = 0.722 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DRA	NM_019111.5	c.*122A>G		3_prime_UTR_variant	Exon 5 of 5	ENST00000395388.7	NP_061984.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DRA	ENST00000395388.7	c.*122A>G		3_prime_UTR_variant	Exon 5 of 5	6	NM_019111.5	ENSP00000378786.2
HLA-DRA	ENST00000374982.5	c.*122A>G		3_prime_UTR_variant	Exon 5 of 5	6		ENSP00000364121.5

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93623 AN: 151912 Hom.: 29218 Cov.: 31

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.781

Gnomad AMR AF: 0.671

Gnomad ASJ AF: 0.747

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.741

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.651

GnomAD4 exome AF: 0.806 AC: 203 AN: 252 Hom.: 82 Cov.: 0 AF XY: 0.779 AC XY: 106 AN XY: 136

Gnomad4 AFR exome AF: 1.00

Gnomad4 SAS exome AF: 0.833

Gnomad4 NFE exome AF: 0.750

Gnomad4 OTH exome AF: 0.688

GnomAD4 genome AF: 0.616 AC: 93685 AN: 152030 Hom.: 29237 Cov.: 31 AF XY: 0.618 AC XY: 45908 AN XY: 74336

Gnomad4 AFR AF: 0.597

Gnomad4 AMR AF: 0.671

Gnomad4 ASJ AF: 0.747

Gnomad4 EAS AF: 0.707

Gnomad4 SAS AF: 0.742

Gnomad4 FIN AF: 0.518

Gnomad4 NFE AF: 0.605

Gnomad4 OTH AF: 0.653

Alfa AF: 0.618 Hom.: 37807

Bravo AF: 0.627

Asia WGS AF: 0.693 AC: 2411 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	4.7
DANN	Benign	0.46

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: rs7195; hg19: chr6-32412539;