rs1820996

chr15-57041011-T-G

Variant summary

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

The NM_207037.2(TCF12):c.149-22739T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,190 control chromosomes in the GnomAD database, including 3,013 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 (3013 hom., cov: 32)
• Consequence: TCF12 NM_207037.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.579

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TCF12	NM_207037.2	c.149-22739T>G		intron_variant		ENST00000333725.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TCF12	ENST00000333725.10	c.149-22739T>G		intron_variant		1	NM_207037.2	P4

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27653 AN: 152072 Hom.: 3016 Cov.: 32

Gnomad AFR AF: 0.0622

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.182 AC: 27653 AN: 152190 Hom.: 3013 Cov.: 32 AF XY: 0.181 AC XY: 13479 AN XY: 74408

Gnomad4 AFR AF: 0.0622

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.187

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.193

Alfa AF: 0.206 Hom.: 455

Bravo AF: 0.174

Asia WGS AF: 0.179 AC: 623 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	5.2
Dann	Benign	0.48

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: rs1820996; hg19: chr15-57333209;