15-56934939-T-C

Variant names:

• chr15-56934939-T-C
• rs2111890
• NM_207037.2:c.148+13841T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_207037.2(TCF12):​c.148+13841T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.725 in 152,046 control chromosomes in the GnomAD database, including 40,313 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 0.73 (40313 hom., cov: 31)
• Consequence: TCF12 NM_207037.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.222
• Publications: 3 publications found

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]

TCF12 Gene-Disease associations (from GenCC):

• TCF12-related craniosynostosis

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), ClinGen
• hypogonadotropic hypogonadism 26 with or without anosmia

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
• Kallmann syndrome

  Inheritance: AR, AD Classification: STRONG Submitted by: Franklin by Genoox
• isolated brachycephaly

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• isolated plagiocephaly

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207037.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF12	NM_207037.2	MANE Select	c.148+13841T>C		intron	N/A	NP_996920.1	Q99081-3
	TCF12	NM_001322151.2		c.148+13841T>C		intron	N/A	NP_001309080.1	Q99081-3
	TCF12	NM_001322159.3		c.148+13841T>C		intron	N/A	NP_001309088.1	Q99081-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCF12	ENST00000333725.10	TSL:1 MANE Select	c.148+13841T>C		intron	N/A	ENSP00000331057.6	Q99081-3
	TCF12	ENST00000267811.9	TSL:1	c.148+13841T>C		intron	N/A	ENSP00000267811.5	Q99081-1
	TCF12	ENST00000557843.5	TSL:1	c.148+13841T>C		intron	N/A	ENSP00000453737.1	Q99081-1

Frequencies

GnomAD3 genomes AF: 0.725 AC: 110197 AN: 151928 Hom.: 40290 Cov.: 31

Gnomad AFR AF: 0.635

Gnomad AMI AF: 0.804

Gnomad AMR AF: 0.749

Gnomad ASJ AF: 0.799

Gnomad EAS AF: 0.787

Gnomad SAS AF: 0.782

Gnomad FIN AF: 0.767

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.755

Gnomad OTH AF: 0.724

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

GnomAD4 genome AF: 0.725 AC: 110264 AN: 152046 Hom.: 40313 Cov.: 31 AF XY: 0.729 AC XY: 54178 AN XY: 74350

African (AFR) AF: 0.635 AC: 26309 AN: 41430

American (AMR) AF: 0.750 AC: 11457 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.799 AC: 2773 AN: 3470

East Asian (EAS) AF: 0.788 AC: 4068 AN: 5164

South Asian (SAS) AF: 0.782 AC: 3764 AN: 4814

European-Finnish (FIN) AF: 0.767 AC: 8118 AN: 10588

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.755 AC: 51300 AN: 67980

Other (OTH) AF: 0.724 AC: 1527 AN: 2110

Alfa AF: 0.746 Hom.: 109206

Bravo AF: 0.721

Asia WGS AF: 0.768 AC: 2670 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.9
DANN	Benign	0.58
PhyloP100		-0.22
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2111890; hg19: chr15-57227137;