rs1059655

Positions:

• chr6-30493308-G-A
• chr6-30493308-G-C
• chr6-30493308-G-T

Variant summary

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

The NM_005516.6(HLA-E):​c.*562G>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 0.728 in 152,038 control chromosomes in the GnomAD database, including 40,733 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 0.73 (40732 hom., cov: 31)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: HLA-E NM_005516.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

Genes affected

HLA-E (HGNC:4962): (major histocompatibility complex, class I, E) HLA-E belongs to the HLA class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. HLA-E binds a restricted subset of peptides derived from the leader peptides of other class I molecules. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the alpha1 and alpha2 domains, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region, and exons 6 and 7 encode the cytoplasmic tail. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-E	NM_005516.6	c.*562G>A		3_prime_UTR_variant	8/8	ENST00000376630.5	NP_005507.3
HLA-E	XM_017010807.2	c.*562G>A		3_prime_UTR_variant	7/7		XP_016866296.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-E	ENST00000376630.5	c.*562G>A		3_prime_UTR_variant	8/8	6	NM_005516.6	ENSP00000365817.4

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110652 AN: 151918 Hom.: 40683 Cov.: 31

Gnomad AFR AF: 0.837

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.832

Gnomad EAS AF: 0.699

Gnomad SAS AF: 0.825

Gnomad FIN AF: 0.681

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.726

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.728 AC: 110757 AN: 152036 Hom.: 40732 Cov.: 31 AF XY: 0.726 AC XY: 53907 AN XY: 74282

Gnomad4 AFR AF: 0.837

Gnomad4 AMR AF: 0.652

Gnomad4 ASJ AF: 0.832

Gnomad4 EAS AF: 0.698

Gnomad4 SAS AF: 0.826

Gnomad4 FIN AF: 0.681

Gnomad4 NFE AF: 0.676

Gnomad4 OTH AF: 0.729

Alfa AF: 0.696 Hom.: 5832

Bravo AF: 0.731

Asia WGS AF: 0.783 AC: 2723 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.73
DANN	Benign	0.25

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: rs1059655; hg19: chr6-30461085;