dbSNP rs1064017: TCL1B:p.Gly93Arg (chr14-95690850-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.351

Publications

31 publications found

Variant links:

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]

TCL1B links:

ENSG00000259084 (HGNC:):

ENSG00000259084 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_004918.4, 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 (MetaRNN=3.3903122E-4).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004918.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCL1B	NM_004918.4	MANE Select	c.277G>A	p.Gly93Arg	missense	Exon 2 of 4	NP_004909.1	O95988

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TCL1B	ENST00000340722.8	TSL:1 MANE Select	c.277G>A	p.Gly93Arg	missense	Exon 2 of 4	ENSP00000343223.6	O95988
ENSG00000259084	ENST00000461160.5	TSL:1	n.2751G>A		non_coding_transcript_exon	Exon 6 of 8
TCL1B	ENST00000464815.5	TSL:1	n.307G>A		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes

AF:

0.363

AC:

55154

AN:

152014

Hom.:

10792

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.414

AC XY:

301303

AN XY:

727146

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

20825

41650

62474

83299

104124

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14838

29676

44514

59352

74190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.363

AC:

55174

AN:

152132

Hom.:

10793

Cov.:

AF XY:

0.353

AC XY:

26222

AN XY:

74366

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1759

3518

5277

7036

8795

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

536

1072

1608

2144

2680

<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:

0.418

Hom.:

38997

Bravo

AF:

0.363

Asia WGS

AF:

0.219

AC:

761

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.023

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.54

MetaRNN

Benign

0.00034

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.6

PhyloP100

0.35

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.7

REVEL

Benign

0.071

Sift

Benign

0.89

Sift4G

Benign

0.46

Varity_R

0.074

gMVP

0.19

Mutation Taster

=88/12

polymorphism (auto)

(source)

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

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over