21-36460323-G-T

Variant names:

• chr21-36460323-G-T
• rs219781
• ENST00000454980.1:n.220G>T

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.328
• Publications: 15 publications found

Genes affected

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

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

ACMG classification

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	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.: 32

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: 7 AN: 36 Hom.: 3 Cov.: 0 AF XY: 0.0625 AC XY: 1 AN XY: 16

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.233 AC: 7 AN: 30

Other (OTH) AF: 0.00 AC: 0 AN: 4

⚠️ 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.

GnomAD4 genome AF: 0.246 AC: 37487 AN: 152094 Hom.: 4902 Cov.: 32 AF XY: 0.240 AC XY: 17829 AN XY: 74370

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: 39 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: 96 AN: 294

European-Non Finnish (NFE) AF: 0.251 AC: 17063 AN: 67960

Other (OTH) AF: 0.258 AC: 543 AN: 2108

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
DANN	Benign	0.77
PhyloP100		-0.33

Splicing

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

Other links and lift over

dbSNP: rs219781; hg19: chr21-37832621;