17-72411715-C-T

Position:

• chr17-72411715-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000457958.7(LINC00511):​n.137-6899G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 151,966 control chromosomes in the GnomAD database, including 12,477 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 0.39 (12477 hom., cov: 32)
• Consequence: LINC00511 ENST00000457958.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.823

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LINC00673	NR_036488.1	n.763-6899G>A		intron_variant
LINC00673	NR_137280.2	n.931-6899G>A		intron_variant
LINC00673	NR_137281.2	n.1028-6899G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LINC00511	ENST00000457958.7	n.137-6899G>A		intron_variant		1
LINC00511	ENST00000453722.6	n.763-10294G>A		intron_variant		2
LINC00511	ENST00000577828.6	n.398-6899G>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59433 AN: 151848 Hom.: 12483 Cov.: 32

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.335

Gnomad EAS AF: 0.814

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.440

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.390

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

GnomAD4 genome AF: 0.391 AC: 59442 AN: 151966 Hom.: 12477 Cov.: 32 AF XY: 0.396 AC XY: 29421 AN XY: 74268

Gnomad4 AFR AF: 0.441

Gnomad4 AMR AF: 0.305

Gnomad4 ASJ AF: 0.335

Gnomad4 EAS AF: 0.813

Gnomad4 SAS AF: 0.429

Gnomad4 FIN AF: 0.440

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.389

Alfa AF: 0.356 Hom.: 10461

Bravo AF: 0.390

Asia WGS AF: 0.561 AC: 1948 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.27
DANN	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3744311; hg19: chr17-70407856;