17-72411715-C-T

Variant names:

• chr17-72411715-C-T
• rs3744311
• ENST00000457958.7:n.137-6899G>A

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000457958.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINC00673	NR_036488.1		n.763-6899G>A		intron	N/A
	LINC00673	NR_137280.2		n.931-6899G>A		intron	N/A
	LINC00673	NR_137281.2		n.1028-6899G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINC00511	ENST00000457958.7	TSL:1	n.137-6899G>A		intron	N/A
	LINC00511	ENST00000453722.6	TSL:2	n.763-10294G>A		intron	N/A
	LINC00511	ENST00000577828.6	TSL:3	n.398-6899G>A		intron	N/A

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

African (AFR) AF: 0.441 AC: 18274 AN: 41430

American (AMR) AF: 0.305 AC: 4659 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.335 AC: 1161 AN: 3468

East Asian (EAS) AF: 0.813 AC: 4203 AN: 5168

South Asian (SAS) AF: 0.429 AC: 2064 AN: 4806

European-Finnish (FIN) AF: 0.440 AC: 4637 AN: 10548

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.343 AC: 23317 AN: 67936

Other (OTH) AF: 0.389 AC: 821 AN: 2110

Alfa AF: 0.368 Hom.: 30742

Bravo AF: 0.390

Asia WGS AF: 0.561 AC: 1948 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.27
DANN	Benign	0.67
PhyloP100		-0.82

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3744311;

hg19: chr17-70407856;