rs8084175

Positions:

• chr18-79717515-C-T

Variant summary

Our verdict is Benign. Variant got -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:3
• Conservation: PhyloP100: -0.383

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 -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 id is 259523.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-79717515-C-T is described in Lovd as [Benign].
• 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/exons	MANE	UniProt
CTDP1	NM_004715.5	c.2069-20C>T		intron_variant		ENST00000613122.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTDP1	ENST00000613122.5	c.2069-20C>T		intron_variant		1	NM_004715.5	P1
CTDP1	ENST00000075430.11	c.2069-20C>T		intron_variant		1
CTDP1	ENST00000591598.5	c.1865-20C>T		intron_variant		1
CTDP1	ENST00000299543.9	c.691-20C>T		intron_variant		5

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

GnomAD3 exomes AF: 0.136 AC: 33620 AN: 248056 Hom.: 2769 AF XY: 0.136 AC XY: 18293 AN XY: 134494

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 SAS exome AF: 0.0730

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

Gnomad4 AFR exome AF: 0.0274

Gnomad4 AMR exome AF: 0.0810

Gnomad4 ASJ exome AF: 0.103

Gnomad4 EAS exome AF: 0.0932

Gnomad4 SAS exome AF: 0.0743

Gnomad4 FIN exome AF: 0.185

Gnomad4 NFE exome AF: 0.193

Gnomad4 OTH exome AF: 0.161

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

Gnomad4 AFR AF: 0.0331

Gnomad4 AMR AF: 0.0937

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.0683

Gnomad4 FIN AF: 0.177

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.108

Alfa AF: 0.151 Hom.: 363

Bravo AF: 0.116

Asia WGS AF: 0.0860 AC: 301 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.3
DANN	Benign	0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs8084175; hg19: chr18-77477515; COSMIC: COSV50002444;