Genetic Variant BTG1:p.Ala18Ser (chr12-92145484-C-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001731.3(BTG1):c.52G>T(p.Ala18Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

BTG1
NM_001731.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.70

Publications

1 publications found

Variant links:

Genes affected

BTG1 (HGNC:1130): (BTG anti-proliferation factor 1) This gene is a member of an anti-proliferative gene family that regulates cell growth and differentiation. Expression of this gene is highest in the G0/G1 phases of the cell cycle and downregulated when cells progressed through G1. The encoded protein interacts with several nuclear receptors, and functions as a coactivator of cell differentiation. This locus has been shown to be involved in a t(8;12)(q24;q22) chromosomal translocation in a case of B-cell chronic lymphocytic leukemia. [provided by RefSeq, Oct 2008]

BTG1 links:

BTG1-DT (HGNC:55600): (BTG1 divergent transcript)

BTG1-DT links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.883

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001731.3. 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
	BTG1	NM_001731.3	MANE Select	c.52G>T	p.Ala18Ser	missense	Exon 1 of 2	NP_001722.1	P62324

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BTG1	ENST00000256015.5	TSL:1 MANE Select	c.52G>T	p.Ala18Ser	missense	Exon 1 of 2	ENSP00000256015.3	P62324
BTG1-DT	ENST00000847949.1		n.201C>A		non_coding_transcript_exon	Exon 1 of 4
BTG1-DT	ENST00000847954.1		n.112C>A		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

223962

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1434906

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

713962

African (AFR)

AF:

0.00

AC:

AN:

29876

American (AMR)

AF:

0.00

AC:

AN:

42214

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25138

East Asian (EAS)

AF:

0.00

AC:

AN:

35616

South Asian (SAS)

AF:

0.00

AC:

AN:

83732

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53154

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5662

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1100388

Other (OTH)

AF:

0.00

AC:

AN:

59126

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.83

BayesDel_addAF

Benign

-0.013

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.57

Eigen

Pathogenic

0.70

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.94

M_CAP

Pathogenic

0.70

MetaRNN

Pathogenic

0.88

MetaSVM

Benign

-0.42

MutationAssessor

Pathogenic

3.4

PhyloP100

6.7

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-2.3

REVEL

Uncertain

0.38

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.030

Polyphen

0.86

Vest4

0.64

MutPred

0.70

Gain of catalytic residue at I15 (P = 0.0011)

MVP

0.43

MPC

1.6

ClinPred

0.99

GERP RS

3.9

PromoterAI

-0.019

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

Varity_R

0.67

gMVP

0.68

Mutation Taster

=59/41

polymorphism

(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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over