rs4150756

Positions:

• chr13-113623226-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000375370.10(TFDP1):​c.126C>T​(p.Leu42=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00569 in 1,613,614 control chromosomes in the GnomAD database, including 287 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 0.011 (40 hom., cov: 33)
  • Exomes 𝑓: 0.0052 (247 hom.)
• Consequence: TFDP1 ENST00000375370.10 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62

Genes affected

TFDP1 (HGNC:11749): (transcription factor Dp-1) This gene encodes a member of a family of transcription factors that heterodimerize with E2F proteins to enhance their DNA-binding activity and promote transcription from E2F target genes. The encoded protein functions as part of this complex to control the transcriptional activity of numerous genes involved in cell cycle progression from G1 to S phase. Alternative splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 1, 15, and X.[provided by RefSeq, Jan 2009]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP7: Synonymous conserved (PhyloP=-1.62 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFDP1	NM_007111.5	c.126C>T	p.Leu42=	synonymous_variant	4/12	ENST00000375370.10	NP_009042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFDP1	ENST00000375370.10	c.126C>T	p.Leu42=	synonymous_variant	4/12	1	NM_007111.5	ENSP00000364519	P1

Frequencies

GnomAD3 genomes AF: 0.0105 AC: 1604 AN: 152208 Hom.: 40 Cov.: 33

Gnomad AFR AF: 0.0159

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.00635

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.0139

Gnomad FIN AF: 0.00424

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00220

Gnomad OTH AF: 0.0110

GnomAD3 exomes AF: 0.0129 AC: 3227 AN: 250020 Hom.: 168 AF XY: 0.0122 AC XY: 1648 AN XY: 135160

Gnomad AFR exome AF: 0.0154

Gnomad AMR exome AF: 0.00215

Gnomad ASJ exome AF: 0.000399

Gnomad EAS exome AF: 0.123

Gnomad SAS exome AF: 0.0105

Gnomad FIN exome AF: 0.00338

Gnomad NFE exome AF: 0.00187

Gnomad OTH exome AF: 0.00786

GnomAD4 exome AF: 0.00518 AC: 7563 AN: 1461288 Hom.: 247 Cov.: 31 AF XY: 0.00529 AC XY: 3844 AN XY: 726852

Gnomad4 AFR exome AF: 0.0170

Gnomad4 AMR exome AF: 0.00215

Gnomad4 ASJ exome AF: 0.000498

Gnomad4 EAS exome AF: 0.0889

Gnomad4 SAS exome AF: 0.0104

Gnomad4 FIN exome AF: 0.00311

Gnomad4 NFE exome AF: 0.00138

Gnomad4 OTH exome AF: 0.0121

GnomAD4 genome AF: 0.0106 AC: 1621 AN: 152326 Hom.: 40 Cov.: 33 AF XY: 0.0110 AC XY: 818 AN XY: 74478

Gnomad4 AFR AF: 0.0162

Gnomad4 AMR AF: 0.00634

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.0137

Gnomad4 FIN AF: 0.00424

Gnomad4 NFE AF: 0.00220

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.00508 Hom.: 7

Bravo AF: 0.0118

Asia WGS AF: 0.0520 AC: 180 AN: 3478

EpiCase AF: 0.00322

EpiControl AF: 0.00237

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.52
DANN	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs4150756; hg19: chr13-114277541; COSMIC: COSV64739546;