rs2921430

Positions:

• chr15-57289215-T-C

Variant summary

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

The NM_207037.2(TCF12):​c.*3070T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,218 control chromosomes in the GnomAD database, including 3,177 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 0.18 (3177 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: TCF12 NM_207037.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.86

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCF12	NM_207037.2	c.*3070T>C		3_prime_UTR_variant	21/21	ENST00000333725.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCF12	ENST00000333725.10	c.*3070T>C		3_prime_UTR_variant	21/21	1	NM_207037.2	P4
TCF12	ENST00000267811.9	c.*3070T>C		3_prime_UTR_variant	20/20	1		A1
TCF12	ENST00000560836.1	c.*11+6617T>C		intron_variant		3
TCF12	ENST00000560948.1	c.*12-1614T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.184 AC: 28019 AN: 152100 Hom.: 3178 Cov.: 33

Gnomad AFR AF: 0.0584

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.224

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.246

Gnomad OTH AF: 0.197

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.184 AC: 28019 AN: 152218 Hom.: 3177 Cov.: 33 AF XY: 0.184 AC XY: 13672 AN XY: 74426

Gnomad4 AFR AF: 0.0584

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.224

Gnomad4 NFE AF: 0.246

Gnomad4 OTH AF: 0.198

Alfa AF: 0.226 Hom.: 1941

Bravo AF: 0.176

Asia WGS AF: 0.181 AC: 630 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	13
DANN	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2921430; hg19: chr15-57581413;