rs7194

Positions:

• chr6-32444703-G-A
• chr6-32444703-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 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. Variant has been reported in Lovd as Benign (no stars).

• 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

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 6-32444703-G-A is Benign according to our data. Variant chr6-32444703-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DRA	NM_019111.5	c.*63G>A		3_prime_UTR_variant	5/5	ENST00000395388.7	NP_061984.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DRA	ENST00000395388.7	c.*63G>A		3_prime_UTR_variant	5/5		NM_019111.5	ENSP00000378786	P1
HLA-DRA	ENST00000374982.5	c.*63G>A		3_prime_UTR_variant	5/5			ENSP00000364121

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

Gnomad4 NFE exome AF: 0.500

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

Gnomad4 AFR AF: 0.597

Gnomad4 AMR AF: 0.672

Gnomad4 ASJ AF: 0.747

Gnomad4 EAS AF: 0.707

Gnomad4 SAS AF: 0.743

Gnomad4 FIN AF: 0.517

Gnomad4 NFE AF: 0.605

Gnomad4 OTH AF: 0.653

Alfa AF: 0.624 Hom.: 35122

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	-0.84
CADD	Benign	0.91
DANN	Benign	0.22

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: rs7194; hg19: chr6-32412480;