rs1064017

Positions:

• chr14-95690850-G-A
• chr14-95690850-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004918.4(TCL1B):​c.277G>A​(p.Gly93Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 1,613,890 control chromosomes in the GnomAD database, including 142,824 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.36 (10793 hom., cov: 32)
  • Exomes 𝑓: 0.42 (132031 hom.)
• Consequence: TCL1B NM_004918.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.351

Genes affected

TCL1B (HGNC:11649): (TCL1 family AKT coactivator B) Enables protein kinase binding activity and protein serine/threonine kinase activator activity. Involved in positive regulation of peptidyl-serine phosphorylation and positive regulation of protein serine/threonine kinase activity. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000259084 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.3903122E-4).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCL1B	NM_004918.4	c.277G>A	p.Gly93Arg	missense_variant	2/4	ENST00000340722.8	NP_004909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCL1B	ENST00000340722.8	c.277G>A	p.Gly93Arg	missense_variant	2/4	1	NM_004918.4	ENSP00000343223.6

Frequencies

GnomAD3 genomes AF: 0.363 AC: 55154 AN: 152014 Hom.: 10792 Cov.: 32

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.0842

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.400

GnomAD3 exomes AF: 0.356 AC: 89505 AN: 251402 Hom.: 17515 AF XY: 0.362 AC XY: 49133 AN XY: 135878

Gnomad AFR exome AF: 0.276

Gnomad AMR exome AF: 0.314

Gnomad ASJ exome AF: 0.373

Gnomad EAS exome AF: 0.0816

Gnomad SAS exome AF: 0.303

Gnomad FIN exome AF: 0.311

Gnomad NFE exome AF: 0.444

Gnomad OTH exome AF: 0.399

GnomAD4 exome AF: 0.417 AC: 609443 AN: 1461758 Hom.: 132031 Cov.: 57 AF XY: 0.414 AC XY: 301303 AN XY: 727146

Gnomad4 AFR exome AF: 0.277

Gnomad4 AMR exome AF: 0.323

Gnomad4 ASJ exome AF: 0.372

Gnomad4 EAS exome AF: 0.102

Gnomad4 SAS exome AF: 0.304

Gnomad4 FIN exome AF: 0.308

Gnomad4 NFE exome AF: 0.452

Gnomad4 OTH exome AF: 0.396

GnomAD4 genome AF: 0.363 AC: 55174 AN: 152132 Hom.: 10793 Cov.: 32 AF XY: 0.353 AC XY: 26222 AN XY: 74366

Gnomad4 AFR AF: 0.278

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.370

Gnomad4 EAS AF: 0.0838

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.450

Gnomad4 OTH AF: 0.402

Alfa AF: 0.426 Hom.: 29038

Bravo AF: 0.363

TwinsUK AF: 0.453 AC: 1680

ALSPAC AF: 0.455 AC: 1752

ESP6500AA AF: 0.294 AC: 1294

ESP6500EA AF: 0.446 AC: 3832

ExAC AF: 0.357 AC: 43342

Asia WGS AF: 0.219 AC: 761 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.023	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.54	T
MetaRNN	Benign	0.00034	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.6	L
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.071
Sift	Benign	0.89	T
Sift4G	Benign	0.46	T
Polyphen		0.95	P
Vest4		0.14
MutPred		0.15		Gain of MoRF binding (P = 0.0059);
MPC		0.93
ClinPred		0.019	T
GERP RS		0.76
Varity_R		0.074
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1064017; hg19: chr14-96157187; COSMIC: COSV61551753;