rs16977243

Positions:

• chr15-57101807-A-C

Variant summary

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

The NM_207037.2(TCF12):​c.325+9916A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,166 control chromosomes in the GnomAD database, including 4,897 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 0.24 (4897 hom., cov: 33)
• Consequence: TCF12 NM_207037.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.572

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=-0.52).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF12	NM_207037.2	c.325+9916A>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.325+9916A>C		intron_variant		1	NM_207037.2	ENSP00000331057	P4

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35972 AN: 152048 Hom.: 4891 Cov.: 33

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.415

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.237 AC: 35998 AN: 152166 Hom.: 4897 Cov.: 33 AF XY: 0.238 AC XY: 17711 AN XY: 74386

Gnomad4 AFR AF: 0.353

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.415

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.224

Alfa AF: 0.197 Hom.: 1638

Bravo AF: 0.243

Asia WGS AF: 0.318 AC: 1108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	13
DANN	Benign	0.44

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: rs16977243; hg19: chr15-57394005;