rs1064017

Variant names:

• chr14-95690850-G-A
• rs1064017
• NM_004918.4:c.277G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 31 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
TCL1B	NM_004918.4	c.277G>A	p.Gly93Arg	missense_variant	Exon 2 of 4	ENST00000340722.8	NP_004909.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCL1B	ENST00000340722.8	c.277G>A	p.Gly93Arg	missense_variant	Exon 2 of 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

GnomAD2 exomes AF: 0.356 AC: 89505 AN: 251402 AF XY: 0.362

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 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

African (AFR) AF: 0.277 AC: 9258 AN: 33480

American (AMR) AF: 0.323 AC: 14426 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 9722 AN: 26136

East Asian (EAS) AF: 0.102 AC: 4040 AN: 39698

South Asian (SAS) AF: 0.304 AC: 26197 AN: 86248

European-Finnish (FIN) AF: 0.308 AC: 16464 AN: 53418

Middle Eastern (MID) AF: 0.417 AC: 2407 AN: 5766

European-Non Finnish (NFE) AF: 0.452 AC: 502990 AN: 1111900

Other (OTH) AF: 0.396 AC: 23939 AN: 60388

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

African (AFR) AF: 0.278 AC: 11534 AN: 41504

American (AMR) AF: 0.350 AC: 5351 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1283 AN: 3468

East Asian (EAS) AF: 0.0838 AC: 434 AN: 5176

South Asian (SAS) AF: 0.283 AC: 1364 AN: 4818

European-Finnish (FIN) AF: 0.300 AC: 3176 AN: 10584

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.450 AC: 30577 AN: 67982

Other (OTH) AF: 0.402 AC: 846 AN: 2106

Alfa AF: 0.418 Hom.: 38997

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
PhyloP100		0.35
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
Mutation Taster		=88/12	polymorphism (auto)

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

Other links and lift over

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