6-30261680-C-T

Variant names:

• chr6-30261680-C-T
• rs2023478
• ENST00000420110.1:n.988C>T

Variant summary

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

The ENST00000420110.1(HLA-L):​n.988C>T 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 0.269 in 1,363,488 control chromosomes in the GnomAD database, including 55,962 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 0.29 (6651 hom., cov: 31)
  • Exomes 𝑓: 0.27 (49311 hom.)
• Consequence: HLA-L ENST00000420110.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.164
• Publications: 10 publications found

Genes affected

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

HLA-L (HGNC:):

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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-L	NR_027822.1	n.875C>T		non_coding_transcript_exon_variant	Exon 5 of 7
HCG17	NR_052012.1	n.127-7216G>A		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-L	ENST00000420110.1	n.988C>T		non_coding_transcript_exon_variant	Exon 5 of 5	6
HLA-L	ENST00000463348.6	n.884C>T		non_coding_transcript_exon_variant	Exon 5 of 7	6
HLA-L	ENST00000482052.7	n.1118C>T		non_coding_transcript_exon_variant	Exon 4 of 6	6

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43273 AN: 151520 Hom.: 6643 Cov.: 31

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.499

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.306

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.309

GnomAD2 exomes AF: 0.322 AC: 80139 AN: 248710 AF XY: 0.321

Gnomad AFR exome AF: 0.293

Gnomad AMR exome AF: 0.469

Gnomad ASJ exome AF: 0.395

Gnomad EAS exome AF: 0.455

Gnomad FIN exome AF: 0.268

Gnomad NFE exome AF: 0.227

Gnomad OTH exome AF: 0.318

GnomAD4 exome AF: 0.267 AC: 323531 AN: 1211850 Hom.: 49311 Cov.: 22 AF XY: 0.272 AC XY: 167325 AN XY: 614242

African (AFR) AF: 0.295 AC: 8247 AN: 27924

American (AMR) AF: 0.462 AC: 20387 AN: 44104

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 9569 AN: 24492

East Asian (EAS) AF: 0.525 AC: 20170 AN: 38386

South Asian (SAS) AF: 0.455 AC: 37097 AN: 81474

European-Finnish (FIN) AF: 0.265 AC: 13805 AN: 52100

Middle Eastern (MID) AF: 0.317 AC: 1664 AN: 5246

European-Non Finnish (NFE) AF: 0.223 AC: 197420 AN: 886320

Other (OTH) AF: 0.293 AC: 15172 AN: 51804

GnomAD4 genome AF: 0.286 AC: 43315 AN: 151638 Hom.: 6651 Cov.: 31 AF XY: 0.292 AC XY: 21663 AN XY: 74082

African (AFR) AF: 0.287 AC: 11848 AN: 41270

American (AMR) AF: 0.390 AC: 5957 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 1408 AN: 3470

East Asian (EAS) AF: 0.489 AC: 2506 AN: 5124

South Asian (SAS) AF: 0.499 AC: 2404 AN: 4820

European-Finnish (FIN) AF: 0.274 AC: 2873 AN: 10488

Middle Eastern (MID) AF: 0.325 AC: 95 AN: 292

European-Non Finnish (NFE) AF: 0.225 AC: 15256 AN: 67900

Other (OTH) AF: 0.311 AC: 654 AN: 2104

Alfa AF: 0.380 Hom.: 8954

Bravo AF: 0.294

Asia WGS AF: 0.532 AC: 1849 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.7
DANN	Benign	0.72
PhyloP100		-0.16

Splicing

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

Other links and lift over

dbSNP: rs2023478; hg19: chr6-30229457;