18-79704170-T-C

Variant names:

• chr18-79704170-T-C
• rs3786228
• NM_004715.5:c.622-597T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004715.5(CTDP1):​c.622-597T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,180 control chromosomes in the GnomAD database, including 8,763 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (8763 hom., cov: 33)
• Consequence: CTDP1 NM_004715.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.412
• Publications: 14 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTDP1	NM_004715.5	c.622-597T>C		intron_variant	Intron 4 of 12	ENST00000613122.5	NP_004706.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTDP1	ENST00000613122.5	c.622-597T>C		intron_variant	Intron 4 of 12	1	NM_004715.5	ENSP00000484525.2
CTDP1	ENST00000075430.11	c.622-597T>C		intron_variant	Intron 4 of 11	1		ENSP00000075430.7
CTDP1	ENST00000591598.5	c.418-597T>C		intron_variant	Intron 4 of 11	1		ENSP00000465119.1

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47134 AN: 152062 Hom.: 8766 Cov.: 33

Gnomad AFR AF: 0.0847

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.394

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.391

Gnomad OTH AF: 0.340

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.310 AC: 47135 AN: 152180 Hom.: 8763 Cov.: 33 AF XY: 0.316 AC XY: 23538 AN XY: 74398

African (AFR) AF: 0.0847 AC: 3519 AN: 41560

American (AMR) AF: 0.379 AC: 5801 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 1172 AN: 3466

East Asian (EAS) AF: 0.413 AC: 2136 AN: 5170

South Asian (SAS) AF: 0.394 AC: 1899 AN: 4822

European-Finnish (FIN) AF: 0.448 AC: 4753 AN: 10598

Middle Eastern (MID) AF: 0.360 AC: 105 AN: 292

European-Non Finnish (NFE) AF: 0.391 AC: 26573 AN: 67954

Other (OTH) AF: 0.342 AC: 724 AN: 2114

Alfa AF: 0.348 Hom.: 5490

Bravo AF: 0.291

Asia WGS AF: 0.391 AC: 1361 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.27
PhyloP100		-0.41
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: rs3786228; hg19: chr18-77464170;