rs9893303

Variant names:

• chr17-72429677-T-C
• rs9893303
• ENST00000457958.7:n.74-1379A>G

Variant summary

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

The ENST00000457958.7(LINC00511):​n.74-1379A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,212 control chromosomes in the GnomAD database, including 2,555 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 0.16 (2555 hom., cov: 32)
• Consequence: LINC00511 ENST00000457958.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.608
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.282 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINC00673	NR_036488.1		n.700-1379A>G		intron	N/A
	LINC00673	NR_137280.2		n.603-1379A>G		intron	N/A
	LINC00673	NR_137281.2		n.700-1379A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINC00511	ENST00000457958.7	TSL:1	n.74-1379A>G		intron	N/A
	LINC00511	ENST00000453722.6	TSL:2	n.700-1379A>G		intron	N/A
	LINC00511	ENST00000577828.6	TSL:3	n.70-1379A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24961 AN: 152094 Hom.: 2549 Cov.: 32

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.0931

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0789

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.164 AC: 24999 AN: 152212 Hom.: 2555 Cov.: 32 AF XY: 0.161 AC XY: 12020 AN XY: 74428

African (AFR) AF: 0.286 AC: 11875 AN: 41500

American (AMR) AF: 0.0930 AC: 1422 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 404 AN: 3470

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5186

South Asian (SAS) AF: 0.0788 AC: 380 AN: 4822

European-Finnish (FIN) AF: 0.150 AC: 1587 AN: 10606

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8832 AN: 68018

Other (OTH) AF: 0.152 AC: 321 AN: 2110

Alfa AF: 0.136 Hom.: 2611

Bravo AF: 0.165

Asia WGS AF: 0.0500 AC: 173 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.9
DANN	Benign	0.67
PhyloP100		0.61

Splicing

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

Other links and lift over

dbSNP: rs9893303; hg19: chr17-70425818;