12-92145814-T-C

Position:

• chr12-92145814-T-C

Variant summary

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

The ENST00000256015.5(BTG1):​c.-279A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 252,314 control chromosomes in the GnomAD database, including 24,300 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 0.46 (16447 hom., cov: 32)
  • Exomes 𝑓: 0.39 (7853 hom.)
• Consequence: BTG1 ENST00000256015.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.314

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BTG1	NM_001731.3	c.-279A>G		5_prime_UTR_variant	1/2	ENST00000256015.5	NP_001722.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BTG1	ENST00000256015.5	c.-279A>G		5_prime_UTR_variant	1/2	1	NM_001731.3	ENSP00000256015	P1
BTG1-DT	ENST00000501008.2	n.242T>C		non_coding_transcript_exon_variant	1/3	5

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70284 AN: 151812 Hom.: 16421 Cov.: 32

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.455

GnomAD4 exome AF: 0.391 AC: 39238 AN: 100384 Hom.: 7853 Cov.: 0 AF XY: 0.389 AC XY: 18977 AN XY: 48758

Gnomad4 AFR exome AF: 0.468

Gnomad4 AMR exome AF: 0.404

Gnomad4 ASJ exome AF: 0.381

Gnomad4 EAS exome AF: 0.334

Gnomad4 SAS exome AF: 0.509

Gnomad4 FIN exome AF: 0.387

Gnomad4 NFE exome AF: 0.392

Gnomad4 OTH exome AF: 0.415

GnomAD4 genome AF: 0.463 AC: 70365 AN: 151930 Hom.: 16447 Cov.: 32 AF XY: 0.469 AC XY: 34827 AN XY: 74240

Gnomad4 AFR AF: 0.509

Gnomad4 AMR AF: 0.467

Gnomad4 ASJ AF: 0.403

Gnomad4 EAS AF: 0.421

Gnomad4 SAS AF: 0.571

Gnomad4 FIN AF: 0.489

Gnomad4 NFE AF: 0.430

Gnomad4 OTH AF: 0.458

Alfa AF: 0.438 Hom.: 12816

Bravo AF: 0.459

Asia WGS AF: 0.506 AC: 1759 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	5.6
DANN	Benign	0.55

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: rs12694; hg19: chr12-92539590;