18-79679844-G-T

Position:

• chr18-79679844-G-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.-104G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 1,111,442 control chromosomes in the GnomAD database, including 78,371 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (8744 hom., cov: 32)
  • Exomes 𝑓: 0.38 (69627 hom.)
• Consequence: CTDP1 NM_004715.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.287

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=-0.97).
• BP6: Variant 18-79679844-G-T is Benign according to our data. Variant chr18-79679844-G-T is described in ClinVar as [Benign]. Clinvar id is 1226092.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-79679844-G-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTDP1	NM_004715.5	c.-104G>T		5_prime_UTR_variant	1/13	ENST00000613122.5	NP_004706.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTDP1	ENST00000613122	c.-104G>T		5_prime_UTR_variant	1/13	1	NM_004715.5	ENSP00000484525.2
CTDP1	ENST00000075430.11	c.-104G>T		upstream_gene_variant		1		ENSP00000075430.7

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47365 AN: 151618 Hom.: 8746 Cov.: 32

Gnomad AFR AF: 0.0962

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.341

GnomAD4 exome AF: 0.376 AC: 360412 AN: 959708 Hom.: 69627 Cov.: 12 AF XY: 0.376 AC XY: 177635 AN XY: 472610

Gnomad4 AFR exome AF: 0.0879

Gnomad4 AMR exome AF: 0.380

Gnomad4 ASJ exome AF: 0.332

Gnomad4 EAS exome AF: 0.413

Gnomad4 SAS exome AF: 0.376

Gnomad4 FIN exome AF: 0.423

Gnomad4 NFE exome AF: 0.382

Gnomad4 OTH exome AF: 0.359

GnomAD4 genome AF: 0.312 AC: 47366 AN: 151734 Hom.: 8744 Cov.: 32 AF XY: 0.319 AC XY: 23644 AN XY: 74178

Gnomad4 AFR AF: 0.0961

Gnomad4 AMR AF: 0.379

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.423

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.448

Gnomad4 NFE AF: 0.390

Gnomad4 OTH AF: 0.343

Alfa AF: 0.350 Hom.: 1340

Bravo AF: 0.295

Asia WGS AF: 0.386 AC: 1338 AN: 3462

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	10
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs56006341; hg19: chr18-77439844;