chr12-92144126-C-T

Position:

• chr12-92144126-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001731.3(BTG1):​c.470G>A​(p.Arg157Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BTG1 NM_001731.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.52

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BTG1	NM_001731.3	c.470G>A	p.Arg157Lys	missense_variant	2/2	ENST00000256015.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTG1	ENST00000256015.5	c.470G>A	p.Arg157Lys	missense_variant	2/2	1	NM_001731.3	P1
BTG1	ENST00000552315.1	n.496G>A		non_coding_transcript_exon_variant	2/2	3
BTG1	ENST00000673901.1	n.374G>A		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 29, 2023

The c.470G>A (p.R157K) alteration is located in exon 2 (coding exon 2) of the BTG1 gene. This alteration results from a G to A substitution at nucleotide position 470, causing the arginine (R) at amino acid position 157 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Uncertain	0.081	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T;.
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.49	T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.5	M;.
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.18
Sift	Uncertain	0.014	D;D
Sift4G	Benign	0.080	T;.
Polyphen		0.90	P;.
Vest4		0.39
MutPred		0.27		Gain of ubiquitination at R157 (P = 0.0029);.;
MVP		0.63
MPC		1.2
ClinPred		0.97	D
GERP RS		5.8
Varity_R		0.56
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-92537902;