rs8037469

Positions:

• chr15-57028521-C-T

Variant summary

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

The NM_207037.2(TCF12):​c.149-35229C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0594 in 152,114 control chromosomes in the GnomAD database, including 621 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 0.059 (621 hom., cov: 32)
• Consequence: TCF12 NM_207037.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF12	NM_207037.2	c.149-35229C>T		intron_variant		ENST00000333725.10	NP_996920.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCF12	ENST00000333725.10	c.149-35229C>T		intron_variant		1	NM_207037.2	ENSP00000331057	P4

Frequencies

GnomAD3 genomes AF: 0.0593 AC: 9014 AN: 151996 Hom.: 617 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.0451

Gnomad AMR AF: 0.0308

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.0260

Gnomad SAS AF: 0.0229

Gnomad FIN AF: 0.0157

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0147

Gnomad OTH AF: 0.0533

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

GnomAD4 genome AF: 0.0594 AC: 9032 AN: 152114 Hom.: 621 Cov.: 32 AF XY: 0.0579 AC XY: 4308 AN XY: 74362

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.0307

Gnomad4 ASJ AF: 0.00692

Gnomad4 EAS AF: 0.0259

Gnomad4 SAS AF: 0.0231

Gnomad4 FIN AF: 0.0157

Gnomad4 NFE AF: 0.0147

Gnomad4 OTH AF: 0.0528

Alfa AF: 0.0274 Hom.: 79

Bravo AF: 0.0656

Asia WGS AF: 0.0440 AC: 156 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.95
DANN	Benign	0.78

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: rs8037469; hg19: chr15-57320719;