rs140627086

Positions:

• chr18-79717873-G-A
• chr18-79717873-G-C

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_004715.5(CTDP1):​c.2274G>A​(p.Pro758=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00509 in 1,613,568 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0029 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0053 (26 hom.)
• Consequence: CTDP1 NM_004715.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.57

Genes affected

CTDP1 (HGNC:2498): (CTD phosphatase subunit 1) This gene encodes a protein which interacts with the carboxy-terminus of the RAP74 subunit of transcription initiation factor TFIIF, and functions as a phosphatase that processively dephosphorylates the C-terminus of POLR2A (a subunit of RNA polymerase II), making it available for initiation of gene expression. Mutations in this gene are associated with congenital cataracts, facial dysmorphism and neuropathy syndrome (CCFDN). Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Feb 2011]

ACMG classification

Verdict is Benign. Variant got -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 18-79717873-G-A is Benign according to our data. Variant chr18-79717873-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 210803.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-79717873-G-A is described in Lovd as [Likely_benign]. Variant chr18-79717873-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-1.58 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTDP1	NM_004715.5	c.2274G>A	p.Pro758=	synonymous_variant	10/13	ENST00000613122.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTDP1	ENST00000613122.5	c.2274G>A	p.Pro758=	synonymous_variant	10/13	1	NM_004715.5	P1
CTDP1	ENST00000075430.11	c.2274G>A	p.Pro758=	synonymous_variant	10/12	1
CTDP1	ENST00000591598.5	c.2070G>A	p.Pro690=	synonymous_variant	10/12	1
CTDP1	ENST00000299543.9	c.897G>A	p.Pro299=	synonymous_variant	3/4	5

Frequencies

GnomAD3 genomes AF: 0.00288 AC: 438 AN: 152184 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000989

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.00273

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00451

Gnomad OTH AF: 0.00383

GnomAD3 exomes AF: 0.00325 AC: 815 AN: 250840 Hom.: 2 AF XY: 0.00328 AC XY: 445 AN XY: 135736

Gnomad AFR exome AF: 0.00118

Gnomad AMR exome AF: 0.00185

Gnomad ASJ exome AF: 0.00238

Gnomad EAS exome AF: 0.000272

Gnomad SAS exome AF: 0.00212

Gnomad FIN exome AF: 0.00363

Gnomad NFE exome AF: 0.00474

Gnomad OTH exome AF: 0.00360

GnomAD4 exome AF: 0.00531 AC: 7765 AN: 1461266 Hom.: 26 Cov.: 35 AF XY: 0.00519 AC XY: 3772 AN XY: 726976

Gnomad4 AFR exome AF: 0.000956

Gnomad4 AMR exome AF: 0.00152

Gnomad4 ASJ exome AF: 0.00176

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.00250

Gnomad4 FIN exome AF: 0.00337

Gnomad4 NFE exome AF: 0.00623

Gnomad4 OTH exome AF: 0.00470

GnomAD4 genome AF: 0.00289 AC: 440 AN: 152302 Hom.: 1 Cov.: 33 AF XY: 0.00263 AC XY: 196 AN XY: 74474

Gnomad4 AFR AF: 0.000986

Gnomad4 AMR AF: 0.00222

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00269

Gnomad4 FIN AF: 0.00273

Gnomad4 NFE AF: 0.00451

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.00380 Hom.: 0

Bravo AF: 0.00312

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.00442

EpiControl AF: 0.00445

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 17, 2015	- -
Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Apr 12, 2016	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

not provided Benign:3

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	CTDP1: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 28, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.29
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs140627086; hg19: chr18-77477873; COSMIC: COSV99311381;