rs4494480

chr15-57063162-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.149-588A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0477 in 152,272 control chromosomes in the GnomAD database, including 346 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 0.048 (346 hom., cov: 32)
• Consequence: TCF12 NM_207037.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.121

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCF12	NM_207037.2	c.149-588A>G		intron_variant		ENST00000333725.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCF12	ENST00000333725.10	c.149-588A>G		intron_variant		1	NM_207037.2	P4

Frequencies

GnomAD3 genomes AF: 0.0477 AC: 7256 AN: 152154 Hom.: 344 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0272

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.0312

Gnomad SAS AF: 0.0238

Gnomad FIN AF: 0.0157

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0143

Gnomad OTH AF: 0.0478

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

GnomAD4 genome AF: 0.0477 AC: 7267 AN: 152272 Hom.: 346 Cov.: 32 AF XY: 0.0471 AC XY: 3506 AN XY: 74462

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.0271

Gnomad4 ASJ AF: 0.00692

Gnomad4 EAS AF: 0.0310

Gnomad4 SAS AF: 0.0240

Gnomad4 FIN AF: 0.0157

Gnomad4 NFE AF: 0.0143

Gnomad4 OTH AF: 0.0473

Alfa AF: 0.0194 Hom.: 137

Bravo AF: 0.0524

Asia WGS AF: 0.0440 AC: 154 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	15
Dann	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.16		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: rs4494480; hg19: chr15-57355360;