rs438259

Variant names:

• chr6-9030103-G-A
• rs438259
• ENST00000642760.1:n.1054-16317G>A

Variant summary

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

The ENST00000642760.1(HULC):​n.1054-16317G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,040 control chromosomes in the GnomAD database, including 5,820 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 0.27 (5820 hom., cov: 32)
• Consequence: HULC ENST00000642760.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15
• Publications: 12 publications found

Genes affected

HULC (HGNC:34232): (hepatocellular carcinoma up-regulated long non-coding RNA) This gene produces a long RNA that was discovered as upregulated in hepatocellular carcinoma and is associated with cancer progression. Expression of this transcript is regulated by microRNAs and at the transcriptional level by Sp1 family factors. The transcript may regulate gene expression by functioning as a competing RNA for microRNAs. [provided by RefSeq, Dec 2017]

LOC105374914 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.366 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105374914	XR_001743951.1	n.585-16317G>A		intron_variant	Intron 2 of 3
LOC105374914	XR_001743952.1	n.279-16317G>A		intron_variant	Intron 3 of 4
LOC105374914	XR_001743953.1	n.279-16317G>A		intron_variant	Intron 3 of 4
LOC105374914	XR_926450.3	n.401-16317G>A		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HULC	ENST00000642760.1	n.1054-16317G>A		intron_variant	Intron 6 of 9
HULC	ENST00000642798.1	n.821-16317G>A		intron_variant	Intron 4 of 6
HULC	ENST00000642877.1	n.112-16317G>A		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41663 AN: 151922 Hom.: 5812 Cov.: 32

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.280

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.280

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.274 AC: 41696 AN: 152040 Hom.: 5820 Cov.: 32 AF XY: 0.273 AC XY: 20282 AN XY: 74286

African (AFR) AF: 0.264 AC: 10971 AN: 41480

American (AMR) AF: 0.251 AC: 3841 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 800 AN: 3470

East Asian (EAS) AF: 0.380 AC: 1959 AN: 5156

South Asian (SAS) AF: 0.222 AC: 1069 AN: 4816

European-Finnish (FIN) AF: 0.267 AC: 2821 AN: 10552

Middle Eastern (MID) AF: 0.274 AC: 80 AN: 292

European-Non Finnish (NFE) AF: 0.286 AC: 19433 AN: 67964

Other (OTH) AF: 0.277 AC: 585 AN: 2114

Alfa AF: 0.283 Hom.: 22797

Bravo AF: 0.272

Asia WGS AF: 0.263 AC: 915 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.1
DANN	Benign	0.83
PhyloP100		1.2

Splicing

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

Other links and lift over

dbSNP: rs438259; hg19: chr6-9030336;