12-92145814-T-C

Variant names:

• chr12-92145814-T-C
• rs12694
• NM_001731.3:c.-279A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001731.3(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 NM_001731.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.314
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTG1	NM_001731.3	MANE Select	c.-279A>G		5_prime_UTR	Exon 1 of 2	NP_001722.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BTG1	ENST00000256015.5	TSL:1 MANE Select	c.-279A>G		5_prime_UTR	Exon 1 of 2	ENSP00000256015.3
	BTG1-DT	ENST00000501008.2	TSL:5	n.242T>C		non_coding_transcript_exon	Exon 1 of 3
	BTG1-DT	ENST00000847949.1		n.348T>C		non_coding_transcript_exon	Exon 2 of 4

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

African (AFR) AF: 0.468 AC: 1836 AN: 3920

American (AMR) AF: 0.404 AC: 1127 AN: 2792

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 2039 AN: 5350

East Asian (EAS) AF: 0.334 AC: 4062 AN: 12158

South Asian (SAS) AF: 0.509 AC: 537 AN: 1056

European-Finnish (FIN) AF: 0.387 AC: 1078 AN: 2784

Middle Eastern (MID) AF: 0.405 AC: 242 AN: 598

European-Non Finnish (NFE) AF: 0.392 AC: 25158 AN: 64116

Other (OTH) AF: 0.415 AC: 3159 AN: 7610

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

African (AFR) AF: 0.509 AC: 21065 AN: 41422

American (AMR) AF: 0.467 AC: 7141 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 1397 AN: 3466

East Asian (EAS) AF: 0.421 AC: 2168 AN: 5154

South Asian (SAS) AF: 0.571 AC: 2749 AN: 4816

European-Finnish (FIN) AF: 0.489 AC: 5152 AN: 10544

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.430 AC: 29187 AN: 67942

Other (OTH) AF: 0.458 AC: 966 AN: 2108

Alfa AF: 0.446 Hom.: 22863

Bravo AF: 0.459

Asia WGS AF: 0.506 AC: 1759 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	5.6
DANN	Benign	0.55
PhyloP100		0.31
PromoterAI		-0.055	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12694; hg19: chr12-92539590;