17-72588126-C-T

Variant names:

• chr17-72588126-C-T
• rs718073
• ENST00000453722.6:n.602+4077G>A

Variant summary

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

The ENST00000453722.6(LINC00511):​n.602+4077G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 152,080 control chromosomes in the GnomAD database, including 41,335 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 0.72 (41335 hom., cov: 32)
• Consequence: LINC00511 ENST00000453722.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.947
• Publications: 8 publications found

Genes affected

LINC00511 (HGNC:43564): (long intergenic non-protein coding RNA 511)

LINC00673 (HGNC:44354): (long intergenic non-protein coding RNA 673) This gene produces a long non-protein coding RNA that is involved in the regulation of gene expression during tumor progression. This transcript can promote cell proliferation in gastric cancer through interaction with enhancer of zeste 2 and other epigenetic suppressors of gene expression, thereby downregulating target genes including Kruppel like factors 2 and 4. This transcript may also act as a tumor suppressor by promoting interaction between protein tyrosine phosphatase, non-receptor type 11 (Ptpn11) and ubiquitin ligase, resulting in degradation of Ptpn11 and lowered oncogenic signalling. Naturally-occurring variation at this locus results in the formation of a binding site for miR-1231, which negatively regulates activity of this transcript. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2017]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINC00673	NR_036488.1	n.602+4077G>A		intron_variant	Intron 1 of 3
LINC00673	NR_137280.2	n.602+4077G>A		intron_variant	Intron 1 of 3
LINC00673	NR_137281.2	n.602+4077G>A		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LINC00511	ENST00000453722.6	n.602+4077G>A		intron_variant	Intron 1 of 4	2
LINC00511	ENST00000580861.2	n.407+14977G>A		intron_variant	Intron 1 of 4	4
LINC00511	ENST00000581801.7	n.594+4077G>A		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109238 AN: 151962 Hom.: 41317 Cov.: 32

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.849

Gnomad AMR AF: 0.763

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.863

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.844

Gnomad OTH AF: 0.726

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

GnomAD4 genome AF: 0.719 AC: 109302 AN: 152080 Hom.: 41335 Cov.: 32 AF XY: 0.718 AC XY: 53405 AN XY: 74368

African (AFR) AF: 0.479 AC: 19842 AN: 41440

American (AMR) AF: 0.763 AC: 11658 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.791 AC: 2742 AN: 3468

East Asian (EAS) AF: 0.534 AC: 2758 AN: 5164

South Asian (SAS) AF: 0.669 AC: 3222 AN: 4818

European-Finnish (FIN) AF: 0.863 AC: 9134 AN: 10584

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.844 AC: 57427 AN: 68002

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

Alfa AF: 0.790 Hom.: 156682

Bravo AF: 0.699

Asia WGS AF: 0.612 AC: 2129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.61
PhyloP100		-0.95

Splicing

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

Other links and lift over

dbSNP: rs718073; hg19: chr17-70584265;