18-79717515-C-T

Variant names:

• chr18-79717515-C-T
• rs8084175
• NM_004715.5:c.2069-20C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004715.5(CTDP1):​c.2069-20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 1,611,332 control chromosomes in the GnomAD database, including 25,158 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1597 hom., cov: 34)
  • Exomes 𝑓: 0.17 (23561 hom.)
• Consequence: CTDP1 NM_004715.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.383
• Publications: 6 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 18-79717515-C-T is Benign according to our data. Variant chr18-79717515-C-T is described in ClinVar as Benign. ClinVar VariationId is 259523.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTDP1	NM_004715.5	c.2069-20C>T		intron_variant	Intron 8 of 12	ENST00000613122.5	NP_004706.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTDP1	ENST00000613122.5	c.2069-20C>T		intron_variant	Intron 8 of 12	1	NM_004715.5	ENSP00000484525.2
CTDP1	ENST00000075430.11	c.2069-20C>T		intron_variant	Intron 8 of 11	1		ENSP00000075430.7
CTDP1	ENST00000591598.5	c.1865-20C>T		intron_variant	Intron 8 of 11	1		ENSP00000465119.1
CTDP1	ENST00000299543.9	c.689-20C>T		intron_variant	Intron 1 of 3	5		ENSP00000299543.9

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19166 AN: 152092 Hom.: 1598 Cov.: 34

Gnomad AFR AF: 0.0332

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.0938

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.0682

Gnomad FIN AF: 0.177

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.110

GnomAD2 exomes AF: 0.136 AC: 33620 AN: 248056 AF XY: 0.136

Gnomad AFR exome AF: 0.0313

Gnomad AMR exome AF: 0.0789

Gnomad ASJ exome AF: 0.106

Gnomad EAS exome AF: 0.123

Gnomad FIN exome AF: 0.181

Gnomad NFE exome AF: 0.181

Gnomad OTH exome AF: 0.138

GnomAD4 exome AF: 0.172 AC: 251683 AN: 1459122 Hom.: 23561 Cov.: 38 AF XY: 0.169 AC XY: 122971 AN XY: 725900

African (AFR) AF: 0.0274 AC: 915 AN: 33428

American (AMR) AF: 0.0810 AC: 3618 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 2692 AN: 26090

East Asian (EAS) AF: 0.0932 AC: 3699 AN: 39692

South Asian (SAS) AF: 0.0743 AC: 6400 AN: 86168

European-Finnish (FIN) AF: 0.185 AC: 9695 AN: 52478

Middle Eastern (MID) AF: 0.0746 AC: 350 AN: 4692

European-Non Finnish (NFE) AF: 0.193 AC: 214621 AN: 1111672

Other (OTH) AF: 0.161 AC: 9693 AN: 60216

GnomAD4 genome AF: 0.126 AC: 19159 AN: 152210 Hom.: 1597 Cov.: 34 AF XY: 0.123 AC XY: 9121 AN XY: 74424

African (AFR) AF: 0.0331 AC: 1374 AN: 41528

American (AMR) AF: 0.0937 AC: 1433 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 349 AN: 3472

East Asian (EAS) AF: 0.119 AC: 619 AN: 5192

South Asian (SAS) AF: 0.0683 AC: 330 AN: 4834

European-Finnish (FIN) AF: 0.177 AC: 1877 AN: 10604

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12741 AN: 67966

Other (OTH) AF: 0.108 AC: 229 AN: 2114

Alfa AF: 0.149 Hom.: 622

Bravo AF: 0.116

Asia WGS AF: 0.0860 AC: 301 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.3
DANN	Benign	0.56
PhyloP100		-0.38
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs8084175; hg19: chr18-77477515; COSMIC: COSV50002444;