rs1059655

Variant names:

• chr6-30493308-G-A
• rs1059655
• NM_005516.6:c.*562G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005516.6. 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-E	NM_005516.6	MANE Select	c.*562G>A		3_prime_UTR	Exon 8 of 8	NP_005507.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-E	ENST00000376630.5	TSL:6 MANE Select	c.*562G>A		3_prime_UTR	Exon 8 of 8	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

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) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 2 AN: 2

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.837 AC: 34730 AN: 41504

American (AMR) AF: 0.652 AC: 9965 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.832 AC: 2887 AN: 3472

East Asian (EAS) AF: 0.698 AC: 3608 AN: 5166

South Asian (SAS) AF: 0.826 AC: 3981 AN: 4822

European-Finnish (FIN) AF: 0.681 AC: 7166 AN: 10524

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.676 AC: 45968 AN: 67952

Other (OTH) AF: 0.729 AC: 1538 AN: 2110

Alfa AF: 0.697 Hom.: 6517

Bravo AF: 0.731

Asia WGS AF: 0.783 AC: 2723 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.73
DANN	Benign	0.25
PhyloP100		-1.2
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: rs1059655; hg19: chr6-30461085;