15-56921373-G-A

Position:

• chr15-56921373-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_207037.2(TCF12):​c.148+275G>A 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 151,706 control chromosomes in the GnomAD database, including 2,988 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.18 (2988 hom., cov: 31)
• Consequence: TCF12 NM_207037.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.57

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 15-56921373-G-A is Benign according to our data. Variant chr15-56921373-G-A is described in ClinVar as [Benign]. Clinvar id is 1231595.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCF12	NM_207037.2	c.148+275G>A		intron_variant		ENST00000333725.10	NP_996920.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCF12	ENST00000333725.10	c.148+275G>A		intron_variant		1	NM_207037.2	ENSP00000331057	P4

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27615 AN: 151588 Hom.: 2991 Cov.: 31

Gnomad AFR AF: 0.0684

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.224

Gnomad NFE AF: 0.239

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: 27615 AN: 151706 Hom.: 2988 Cov.: 31 AF XY: 0.181 AC XY: 13423 AN XY: 74132

Gnomad4 AFR AF: 0.0684

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.193

Alfa AF: 0.206 Hom.: 450

Bravo AF: 0.174

Asia WGS AF: 0.175 AC: 599 AN: 3426

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.11
DANN	Benign	0.24

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: rs213152; hg19: chr15-57213571;