rs12901270

Positions:

• chr15-57005315-A-C
• chr15-57005315-A-G

Variant summary

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

The NM_207037.2(TCF12):​c.149-58435A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,184 control chromosomes in the GnomAD database, including 4,052 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 0.20 (4052 hom., cov: 32)
• Consequence: TCF12 NM_207037.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0600

Genes affected

TCF12 (HGNC:11623): (transcription factor 12) The protein encoded by this gene is a member of the basic helix-loop-helix (bHLH) E-protein family that recognizes the consensus binding site (E-box) CANNTG. This encoded protein is expressed in many tissues, among them skeletal muscle, thymus, B- and T-cells, and may participate in regulating lineage-specific gene expression through the formation of heterodimers with other bHLH E-proteins. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF12	NM_207037.2	c.149-58435A>C		intron_variant		ENST00000333725.10	NP_996920.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCF12	ENST00000333725.10	c.149-58435A>C		intron_variant		1	NM_207037.2	ENSP00000331057	P4

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30250 AN: 152066 Hom.: 4051 Cov.: 32

Gnomad AFR AF: 0.0493

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.0983

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.197

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.199 AC: 30242 AN: 152184 Hom.: 4052 Cov.: 32 AF XY: 0.196 AC XY: 14612 AN XY: 74402

Gnomad4 AFR AF: 0.0491

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.0987

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.315

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.194

Alfa AF: 0.254 Hom.: 6620

Bravo AF: 0.181

Asia WGS AF: 0.106 AC: 369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.7
DANN	Benign	0.85

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: rs12901270; hg19: chr15-57297513;