Genetic Variant ENST00000454980.1:n.220G>T (chr21-36460323-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000454980.1(LNCTSI):n.220G>T 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 0.246 in 152,130 control chromosomes in the GnomAD database, including 4,905 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 0.25 ( 4902 hom., cov: 32)

Exomes 𝑓: 0.19 ( 3 hom. )

Consequence

LNCTSI
ENST00000454980.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.328

Publications

15 publications found

Variant links:

Genes affected

LNCTSI (HGNC:56660): (lncRNA TGF-beta/SMAD3 pathway interacting)

LNCTSI links:

CLDN14-AS1 (HGNC:55953): (CLDN14 antisense RNA 1)

CLDN14-AS1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000454980.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000454980.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank
CLDN14-AS1	NR_183532.1	n.502G>T	non_coding_transcript_exon	Exon 3 of 3
CLDN14-AS1	NR_183529.1	n.468+14316G>T	intron	N/A
CLDN14-AS1	NR_183530.1	n.468+14316G>T	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
LNCTSI	ENST00000454980.1	TSL:2	n.220G>T	non_coding_transcript_exon	Exon 2 of 2
LNCTSI	ENST00000820009.1		n.122G>T	non_coding_transcript_exon	Exon 2 of 2
LNCTSI	ENST00000428667.2	TSL:5	n.468+14316G>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.246

AC:

37420

AN:

151976

Hom.:

4883

Cov.:

show subpopulations

Gnomad AFR

AF:

0.296

Gnomad AMI

AF:

0.126

Gnomad AMR

AF:

0.227

Gnomad ASJ

AF:

0.258

Gnomad EAS

AF:

0.00751

Gnomad SAS

AF:

0.146

Gnomad FIN

AF:

0.211

Gnomad MID

AF:

0.323

Gnomad NFE

AF:

0.251

Gnomad OTH

AF:

0.260

GnomAD4 exome

AF:

0.194

AC:

AN:

Hom.:

Cov.:

AF XY:

0.0625

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.233

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.246

AC:

37487

AN:

152094

Hom.:

4902

Cov.:

AF XY:

0.240

AC XY:

17829

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.297

AC:

12330

AN:

41496

American (AMR)

AF:

0.227

AC:

3471

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.258

AC:

895

AN:

3470

East Asian (EAS)

AF:

0.00753

AC:

AN:

5180

South Asian (SAS)

AF:

0.146

AC:

704

AN:

4810

European-Finnish (FIN)

AF:

0.211

AC:

2231

AN:

10582

Middle Eastern (MID)

AF:

0.327

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.251

AC:

17063

AN:

67960

Other (OTH)

AF:

0.258

AC:

543

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1408

2817

4225

5634

7042

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

384

768

1152

1536

1920

<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:

0.249

Hom.:

13952

Bravo

AF:

0.248

Asia WGS

AF:

0.109

AC:

382

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.24

(source)

DANN

Benign

0.77

PhyloP100

-0.33

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.

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