rs731652

Positions:

• chr12-92145033-G-A
• chr12-92145033-G-T

Variant summary

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

The NM_001731.3(BTG1):​c.148+355C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 187,566 control chromosomes in the GnomAD database, including 2,338 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.16 (1975 hom., cov: 32)
  • Exomes 𝑓: 0.13 (363 hom.)
• Consequence: BTG1 NM_001731.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BTG1	NM_001731.3	c.148+355C>T		intron_variant		ENST00000256015.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BTG1	ENST00000256015.5	c.148+355C>T		intron_variant		1	NM_001731.3	P1
BTG1	ENST00000552315.1	n.174+27C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23680 AN: 151902 Hom.: 1968 Cov.: 32

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.0976

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.178

GnomAD4 exome AF: 0.131 AC: 4667 AN: 35546 Hom.: 363 Cov.: 2 AF XY: 0.128 AC XY: 2401 AN XY: 18818

Gnomad4 AFR exome AF: 0.0947

Gnomad4 AMR exome AF: 0.222

Gnomad4 ASJ exome AF: 0.138

Gnomad4 EAS exome AF: 0.145

Gnomad4 SAS exome AF: 0.104

Gnomad4 FIN exome AF: 0.172

Gnomad4 NFE exome AF: 0.131

Gnomad4 OTH exome AF: 0.141

GnomAD4 genome AF: 0.156 AC: 23708 AN: 152020 Hom.: 1975 Cov.: 32 AF XY: 0.157 AC XY: 11633 AN XY: 74300

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.194

Gnomad4 SAS AF: 0.0980

Gnomad4 FIN AF: 0.166

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.181

Alfa AF: 0.160 Hom.: 248

Bravo AF: 0.162

Asia WGS AF: 0.139 AC: 485 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.92
DANN	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs731652; hg19: chr12-92538809;