14-95714358-G-T

Variant names:

• chr14-95714358-G-T
• rs2887399
• ENST00000547644.6:n.152+2460G>T

Variant summary

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

The ENST00000547644.6(ENSG00000257275):​n.152+2460G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 151,980 control chromosomes in the GnomAD database, including 5,625 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 0.26 (5625 hom., cov: 32)
• Consequence: ENSG00000257275 ENST00000547644.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0520
• Publications: 24 publications found

Genes affected

ENSG00000257275 (HGNC:):

TCL1A (HGNC:11648): (TCL1 family AKT coactivator A) Overexpression of the TCL1 gene in humans has been implicated in the development of mature T cell leukemia, in which chromosomal rearrangements bring the TCL1 gene in close proximity to the T-cell antigen receptor (TCR)-alpha (MIM 186880) or TCR-beta (MIM 186930) regulatory elements (summarized by Virgilio et al., 1998 [PubMed 9520462]). In normal T cells TCL1 is expressed in CD4-/CD8- cells, but not in cells at later stages of differentiation. TCL1 functions as a coactivator of the cell survival kinase AKT (MIM 164730) (Laine et al., 2000 [PubMed 10983986]).[supplied by OMIM, Jul 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000547644.6. 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
	TCL1A	NM_021966.3	MANE Select	c.-292C>A		upstream_gene	N/A	NP_068801.1
	TCL1A	NM_001098725.2		c.-292C>A		upstream_gene	N/A	NP_001092195.1
	TCL1A	NR_049726.2		n.-233C>A		upstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000257275	ENST00000547644.6	TSL:2	n.152+2460G>T		intron	N/A
	ENSG00000257275	ENST00000553445.5	TSL:3	n.269+2333G>T		intron	N/A
	TCL1A	ENST00000402399.6	TSL:1 MANE Select	c.-292C>A		upstream_gene	N/A	ENSP00000385036.1

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39108 AN: 151862 Hom.: 5617 Cov.: 32

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.277

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.213

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.258 AC: 39156 AN: 151980 Hom.: 5625 Cov.: 32 AF XY: 0.257 AC XY: 19089 AN XY: 74306

African (AFR) AF: 0.396 AC: 16389 AN: 41416

American (AMR) AF: 0.196 AC: 2994 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.277 AC: 959 AN: 3462

East Asian (EAS) AF: 0.112 AC: 579 AN: 5156

South Asian (SAS) AF: 0.212 AC: 1026 AN: 4830

European-Finnish (FIN) AF: 0.230 AC: 2436 AN: 10580

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14042 AN: 67928

Other (OTH) AF: 0.226 AC: 478 AN: 2112

Alfa AF: 0.217 Hom.: 10838

Bravo AF: 0.261

Asia WGS AF: 0.193 AC: 672 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.8
DANN	Benign	0.58
PhyloP100		0.052
PromoterAI		0.0062	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2887399; hg19: chr14-96180695;