rs626169

Positions:

• chr18-79753721-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_004715.5(CTDP1):​c.2817T>C​(p.Asp939=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.979 in 1,614,048 control chromosomes in the GnomAD database, including 777,656 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.91 (64273 hom., cov: 33)
  • Exomes 𝑓: 0.99 (713383 hom.)
• Consequence: CTDP1 NM_004715.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.0560

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 18-79753721-T-C is Benign according to our data. Variant chr18-79753721-T-C is described in ClinVar as [Benign]. Clinvar id is 128865.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-79753721-T-C is described in Lovd as [Benign]. Variant chr18-79753721-T-C is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=0.056 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTDP1	NM_004715.5	c.2817T>C	p.Asp939=	synonymous_variant	13/13	ENST00000613122.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTDP1	ENST00000613122.5	c.2817T>C	p.Asp939=	synonymous_variant	13/13	1	NM_004715.5	P1

Frequencies

GnomAD3 genomes AF: 0.910 AC: 138390 AN: 152116 Hom.: 64241 Cov.: 33

Gnomad AFR AF: 0.701

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.962

Gnomad ASJ AF: 0.912

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.987

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.997

Gnomad OTH AF: 0.923

GnomAD3 exomes AF: 0.971 AC: 243695 AN: 250934 Hom.: 119022 AF XY: 0.977 AC XY: 132613 AN XY: 135766

Gnomad AFR exome AF: 0.701

Gnomad AMR exome AF: 0.980

Gnomad ASJ exome AF: 0.921

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.988

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.997

Gnomad OTH exome AF: 0.975

GnomAD4 exome AF: 0.987 AC: 1442466 AN: 1461814 Hom.: 713383 Cov.: 81 AF XY: 0.988 AC XY: 718243 AN XY: 727214

Gnomad4 AFR exome AF: 0.695

Gnomad4 AMR exome AF: 0.977

Gnomad4 ASJ exome AF: 0.918

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.989

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.997

Gnomad4 OTH exome AF: 0.970

GnomAD4 genome AF: 0.910 AC: 138475 AN: 152234 Hom.: 64273 Cov.: 33 AF XY: 0.913 AC XY: 67951 AN XY: 74436

Gnomad4 AFR AF: 0.701

Gnomad4 AMR AF: 0.963

Gnomad4 ASJ AF: 0.912

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.987

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.997

Gnomad4 OTH AF: 0.924

Alfa AF: 0.952 Hom.: 36940

Bravo AF: 0.897

Asia WGS AF: 0.971 AC: 3376 AN: 3478

EpiCase AF: 0.994

EpiControl AF: 0.994

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Congenital cataracts-facial dysmorphism-neuropathy syndrome Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	5.0
DANN	Benign	0.59

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: rs626169; hg19: chr18-77513721; COSMIC: COSV50007027; COSMIC: COSV50007027;