Genetic Variant ENST00000457958.7:n.928G>A (chr17-72404025-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000457958.7(LINC00511):n.928G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,140 control chromosomes in the GnomAD database, including 2,509 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.17 ( 2509 hom., cov: 31)

Exomes 𝑓: 0.15 ( 0 hom. )

Consequence

LINC00511
ENST00000457958.7 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.460

Publications

73 publications found

Variant links:

Genes affected

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

LINC00511 links:

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]

LINC00673 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.272 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

Gene	Transcript	HGVSc	Effect	Exon Rank
LINC00673	NR_036488.1	n.1554G>A	non_coding_transcript_exon	Exon 4 of 4
LINC00673	NR_137280.2	n.1722G>A	non_coding_transcript_exon	Exon 4 of 4
LINC00673	NR_137281.2	n.1819G>A	non_coding_transcript_exon	Exon 5 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
LINC00511	ENST00000457958.7	TSL:1	n.928G>A	non_coding_transcript_exon	Exon 3 of 3
LINC00511	ENST00000578206.2	TSL:3	n.1034G>A	non_coding_transcript_exon	Exon 2 of 2
LINC00511	ENST00000647593.1		n.992G>A	non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.165

AC:

25124

AN:

151972

Hom.:

2486

Cov.:

show subpopulations

Gnomad AFR

AF:

0.215

Gnomad AMI

AF:

0.0581

Gnomad AMR

AF:

0.278

Gnomad ASJ

AF:

0.0765

Gnomad EAS

AF:

0.231

Gnomad SAS

AF:

0.270

Gnomad FIN

AF:

0.120

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.111

Gnomad OTH

AF:

0.155

GnomAD4 exome

AF:

0.146

AC:

AN:

Hom.:

Cov.:

AF XY:

0.143

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.115

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.165

AC:

25171

AN:

152092

Hom.:

2509

Cov.:

AF XY:

0.170

AC XY:

12628

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.215

AC:

8912

AN:

41458

American (AMR)

AF:

0.279

AC:

4259

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0765

AC:

265

AN:

3466

East Asian (EAS)

AF:

0.231

AC:

1195

AN:

5172

South Asian (SAS)

AF:

0.270

AC:

1301

AN:

4818

European-Finnish (FIN)

AF:

0.120

AC:

1274

AN:

10592

Middle Eastern (MID)

AF:

0.173

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.111

AC:

7525

AN:

67992

Other (OTH)

AF:

0.160

AC:

336

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1043

2087

3130

4174

5217

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

282

564

846

1128

1410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.124

Hom.:

1480

Bravo

AF:

0.177

Asia WGS

AF:

0.316

AC:

1096

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

0.46

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over