rs3094073

Variant names:

• chr6-30263447-G-A
• rs3094073
• ENST00000463348.6:n.1127G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000463348.6(HLA-L):​n.1127G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 526,342 control chromosomes in the GnomAD database, including 4,445 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 0.12 (1215 hom., cov: 32)
  • Exomes 𝑓: 0.12 (3230 hom.)
• Consequence: HLA-L ENST00000463348.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0650
• Publications: 33 publications found

Genes affected

HLA-L (HGNC:):

HLA-L (HGNC:4970): (major histocompatibility complex, class I, L (pseudogene))

HCG18 (HGNC:31337): (HLA complex group 18)

HCG17 (HGNC:31339): (HLA complex group 17)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-L	NR_027822.1	n.1118G>A		non_coding_transcript_exon_variant	Exon 7 of 7
HCG17	NR_052012.1	n.127-8983C>T		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-L	ENST00000463348.6	n.1127G>A		non_coding_transcript_exon_variant	Exon 7 of 7	6
HLA-L	ENST00000701167.1	n.1845G>A		non_coding_transcript_exon_variant	Exon 7 of 7
HLA-L	ENST00000702262.1	n.1331G>A		non_coding_transcript_exon_variant	Exon 8 of 8

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18173 AN: 152072 Hom.: 1209 Cov.: 32

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.0910

Gnomad ASJ AF: 0.0638

Gnomad EAS AF: 0.0493

Gnomad SAS AF: 0.0818

Gnomad FIN AF: 0.0944

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.151

Gnomad OTH AF: 0.100

GnomAD2 exomes AF: 0.116 AC: 28086 AN: 242154 AF XY: 0.118

Gnomad AFR exome AF: 0.103

Gnomad AMR exome AF: 0.104

Gnomad ASJ exome AF: 0.0598

Gnomad EAS exome AF: 0.0506

Gnomad FIN exome AF: 0.0961

Gnomad NFE exome AF: 0.145

Gnomad OTH exome AF: 0.115

GnomAD4 exome AF: 0.121 AC: 45404 AN: 374150 Hom.: 3230 Cov.: 0 AF XY: 0.121 AC XY: 25891 AN XY: 213572

African (AFR) AF: 0.103 AC: 1036 AN: 10016

American (AMR) AF: 0.102 AC: 3530 AN: 34696

Ashkenazi Jewish (ASJ) AF: 0.0629 AC: 714 AN: 11358

East Asian (EAS) AF: 0.0555 AC: 709 AN: 12782

South Asian (SAS) AF: 0.103 AC: 6682 AN: 65144

European-Finnish (FIN) AF: 0.101 AC: 3200 AN: 31772

Middle Eastern (MID) AF: 0.0751 AC: 211 AN: 2808

European-Non Finnish (NFE) AF: 0.145 AC: 27394 AN: 189178

Other (OTH) AF: 0.118 AC: 1928 AN: 16396

GnomAD4 genome AF: 0.120 AC: 18203 AN: 152192 Hom.: 1215 Cov.: 32 AF XY: 0.115 AC XY: 8556 AN XY: 74424

African (AFR) AF: 0.102 AC: 4239 AN: 41534

American (AMR) AF: 0.0909 AC: 1389 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0638 AC: 221 AN: 3466

East Asian (EAS) AF: 0.0496 AC: 257 AN: 5184

South Asian (SAS) AF: 0.0831 AC: 401 AN: 4824

European-Finnish (FIN) AF: 0.0944 AC: 999 AN: 10586

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.151 AC: 10297 AN: 67996

Other (OTH) AF: 0.104 AC: 219 AN: 2108

Alfa AF: 0.141 Hom.: 5546

Bravo AF: 0.119

Asia WGS AF: 0.0750 AC: 262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.6
DANN	Benign	0.35
PhyloP100		-0.065

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3094073; hg19: chr6-30231224; COSMIC: COSV69717041;