rs7195

Variant names:

• chr6-32444762-A-G
• rs7195
• NM_019111.5:c.*122A>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.*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
• Publications: 43 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.722 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DRA	NM_019111.5	MANE Select	c.*122A>G		3_prime_UTR	Exon 5 of 5	NP_061984.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DRA	ENST00000395388.7	TSL:6 MANE Select	c.*122A>G		3_prime_UTR	Exon 5 of 5	ENSP00000378786.2	P01903
	HLA-DRA	ENST00000870696.1		c.*852A>G		3_prime_UTR	Exon 4 of 4	ENSP00000540755.1
	HLA-DRA	ENST00000917299.1		c.*126A>G		3_prime_UTR	Exon 5 of 5	ENSP00000587358.1

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

African (AFR) AF: 1.00 AC: 4 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.833 AC: 15 AN: 18

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.813 AC: 161 AN: 198

European-Non Finnish (NFE) AF: 0.750 AC: 12 AN: 16

Other (OTH) AF: 0.688 AC: 11 AN: 16

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

African (AFR) AF: 0.597 AC: 24767 AN: 41474

American (AMR) AF: 0.671 AC: 10251 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.747 AC: 2591 AN: 3470

East Asian (EAS) AF: 0.707 AC: 3647 AN: 5158

South Asian (SAS) AF: 0.742 AC: 3581 AN: 4824

European-Finnish (FIN) AF: 0.518 AC: 5466 AN: 10558

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.605 AC: 41082 AN: 67956

Other (OTH) AF: 0.653 AC: 1376 AN: 2108

Alfa AF: 0.611 Hom.: 107214

Bravo AF: 0.627

Asia WGS AF: 0.693 AC: 2411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.7
DANN	Benign	0.46
PhyloP100		0.20
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: rs7195; hg19: chr6-32412539;