chr18-79717873-G-A

Variant names:

• chr18-79717873-G-A
• rs140627086
• NM_004715.5:c.2274G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_004715.5(CTDP1):​c.2274G>A​(p.Pro758Pro) 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:8
• Conservation: PhyloP100: -1.57
• Publications: 1 publications found

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]

CTDP1 Gene-Disease associations (from GenCC):

• congenital cataracts-facial dysmorphism-neuropathy syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 210803.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.58 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 26 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004715.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTDP1	NM_004715.5	MANE Select	c.2274G>A	p.Pro758Pro	synonymous	Exon 10 of 13	NP_004706.3
	CTDP1	NM_001318511.2		c.2274G>A	p.Pro758Pro	synonymous	Exon 10 of 12	NP_001305440.1
	CTDP1	NM_048368.4		c.2274G>A	p.Pro758Pro	synonymous	Exon 10 of 12	NP_430255.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTDP1	ENST00000613122.5	TSL:1 MANE Select	c.2274G>A	p.Pro758Pro	synonymous	Exon 10 of 13	ENSP00000484525.2
	CTDP1	ENST00000075430.11	TSL:1	c.2274G>A	p.Pro758Pro	synonymous	Exon 10 of 12	ENSP00000075430.7
	CTDP1	ENST00000591598.5	TSL:1	c.2070G>A	p.Pro690Pro	synonymous	Exon 10 of 12	ENSP00000465119.1

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

GnomAD2 exomes AF: 0.00325 AC: 815 AN: 250840 AF XY: 0.00328

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 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

African (AFR) AF: 0.000956 AC: 32 AN: 33478

American (AMR) AF: 0.00152 AC: 68 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00176 AC: 46 AN: 26130

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39696

South Asian (SAS) AF: 0.00250 AC: 216 AN: 86258

European-Finnish (FIN) AF: 0.00337 AC: 178 AN: 52858

Middle Eastern (MID) AF: 0.00173 AC: 10 AN: 5768

European-Non Finnish (NFE) AF: 0.00623 AC: 6927 AN: 1111970

Other (OTH) AF: 0.00470 AC: 284 AN: 60388

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

African (AFR) AF: 0.000986 AC: 41 AN: 41578

American (AMR) AF: 0.00222 AC: 34 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5172

South Asian (SAS) AF: 0.00269 AC: 13 AN: 4834

European-Finnish (FIN) AF: 0.00273 AC: 29 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00451 AC: 307 AN: 68012

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.00370 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:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Apr 12, 2016

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Jun 17, 2015

Eurofins Ntd Llc (ga)

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:4

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Sep 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CTDP1: BP4, BP7, BS2

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.29
DANN	Benign	0.66
PhyloP100		-1.6
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs140627086; hg19: chr18-77477873; COSMIC: COSV99311381;