rs7194

Variant names:

• chr6-32444703-G-A
• rs7194
• NM_019111.5:c.*63G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-32444703-G-A
• chr6-32444703-G-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.*63G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 151,856 control chromosomes in the GnomAD database, including 29,199 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 (29198 hom., cov: 30)
  • Exomes 𝑓: 0.75 (1 hom.)
• Consequence: HLA-DRA NM_019111.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.779
• Publications: 59 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 (SAS) allele frequency at 95% confidence interval = 0.723 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.*63G>A		3_prime_UTR	Exon 5 of 5	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.*63G>A		3_prime_UTR	Exon 5 of 5	ENSP00000378786.2
	HLA-DRA	ENST00000374982.5	TSL:6	c.*63G>A		3_prime_UTR	Exon 5 of 5	ENSP00000364121.5
	ENSG00000299747	ENST00000766007.1		n.163-6443C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93521 AN: 151734 Hom.: 29179 Cov.: 30

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.782

Gnomad AMR AF: 0.672

Gnomad ASJ AF: 0.747

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.605

Gnomad OTH AF: 0.651

GnomAD4 exome AF: 0.750 AC: 3 AN: 4 Hom.: 1 Cov.: 0 AF XY: 0.750 AC XY: 3 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

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

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.616 AC: 93583 AN: 151852 Hom.: 29198 Cov.: 30 AF XY: 0.617 AC XY: 45827 AN XY: 74218

African (AFR) AF: 0.597 AC: 24719 AN: 41404

American (AMR) AF: 0.672 AC: 10260 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.747 AC: 2589 AN: 3466

East Asian (EAS) AF: 0.707 AC: 3637 AN: 5146

South Asian (SAS) AF: 0.743 AC: 3569 AN: 4802

European-Finnish (FIN) AF: 0.517 AC: 5440 AN: 10518

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

European-Non Finnish (NFE) AF: 0.605 AC: 41069 AN: 67928

Other (OTH) AF: 0.653 AC: 1378 AN: 2110

Alfa AF: 0.622 Hom.: 59454

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	-0.84
CADD	Benign	0.91
DANN	Benign	0.22
PhyloP100		-0.78
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: rs7194; hg19: chr6-32412480;