chr6-30489955-T-C

Variant names:

• chr6-30489955-T-C
• rs1059510
• NM_005516.6:c.294T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005516.6(HLA-E):​c.294T>C​(p.Asn98Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 1,611,200 control chromosomes in the GnomAD database, including 380,148 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 0.70 (37143 hom., cov: 30)
  • Exomes 𝑓: 0.68 (343005 hom.)
• Consequence: HLA-E NM_005516.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.405
• Publications: 41 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.15).
• BP7: Synonymous conserved (PhyloP=0.405 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.8 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-E	NM_005516.6	c.294T>C	p.Asn98Asn	synonymous_variant	Exon 2 of 8	ENST00000376630.5	NP_005507.3
HLA-E	XM_017010807.2	c.417T>C	p.Asn139Asn	synonymous_variant	Exon 1 of 7		XP_016866296.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-E	ENST00000376630.5	c.294T>C	p.Asn98Asn	synonymous_variant	Exon 2 of 8	6	NM_005516.6	ENSP00000365817.4
HLA-E	ENST00000484194.1	n.316T>C		non_coding_transcript_exon_variant	Exon 2 of 2	6
HLA-E	ENST00000493699.1	n.444T>C		non_coding_transcript_exon_variant	Exon 1 of 3	6

Frequencies

GnomAD3 genomes AF: 0.698 AC: 105910 AN: 151808 Hom.: 37108 Cov.: 30

Gnomad AFR AF: 0.747

Gnomad AMI AF: 0.757

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.795

Gnomad EAS AF: 0.716

Gnomad SAS AF: 0.821

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.661

Gnomad OTH AF: 0.688

GnomAD2 exomes AF: 0.703 AC: 172639 AN: 245680 AF XY: 0.707

Gnomad AFR exome AF: 0.746

Gnomad AMR exome AF: 0.705

Gnomad ASJ exome AF: 0.784

Gnomad EAS exome AF: 0.724

Gnomad FIN exome AF: 0.676

Gnomad NFE exome AF: 0.662

Gnomad OTH exome AF: 0.694

GnomAD4 exome AF: 0.684 AC: 997762 AN: 1459274 Hom.: 343005 Cov.: 52 AF XY: 0.688 AC XY: 499391 AN XY: 725808

African (AFR) AF: 0.752 AC: 25173 AN: 33454

American (AMR) AF: 0.700 AC: 31294 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.792 AC: 20647 AN: 26064

East Asian (EAS) AF: 0.723 AC: 28691 AN: 39682

South Asian (SAS) AF: 0.809 AC: 69716 AN: 86202

European-Finnish (FIN) AF: 0.678 AC: 35388 AN: 52218

Middle Eastern (MID) AF: 0.794 AC: 4513 AN: 5684

European-Non Finnish (NFE) AF: 0.666 AC: 739432 AN: 1110972

Other (OTH) AF: 0.711 AC: 42908 AN: 60314

GnomAD4 genome AF: 0.698 AC: 106004 AN: 151926 Hom.: 37143 Cov.: 30 AF XY: 0.698 AC XY: 51801 AN XY: 74252

African (AFR) AF: 0.747 AC: 30984 AN: 41466

American (AMR) AF: 0.663 AC: 10115 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.795 AC: 2758 AN: 3470

East Asian (EAS) AF: 0.715 AC: 3664 AN: 5126

South Asian (SAS) AF: 0.821 AC: 3959 AN: 4822

European-Finnish (FIN) AF: 0.688 AC: 7258 AN: 10548

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.661 AC: 44902 AN: 67920

Other (OTH) AF: 0.691 AC: 1459 AN: 2110

Alfa AF: 0.685 Hom.: 56790

Bravo AF: 0.698

Asia WGS AF: 0.783 AC: 2723 AN: 3478

EpiCase AF: 0.678

EpiControl AF: 0.676

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	7.5
DANN	Benign	0.61
PhyloP100		0.41
PromoterAI		-0.0096	Neutral
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: rs1059510; hg19: chr6-30457732; COSMIC: COSV64927479; COSMIC: COSV64927479;