Genetic Variant XM_047437922.1:c.236G>T (chr18-79679637-G-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The XM_047437922.1(CTDP1):c.236G>T(p.Gly79Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 491,998 control chromosomes in the GnomAD database, including 5,690 homozygotes. In-silico tool predicts a benign outcome for this variant. 4/4 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1540 hom., cov: 32)

Exomes 𝑓: 0.14 ( 4150 hom. )

Consequence

CTDP1
XM_047437922.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.578

Variant links:

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 links:

CTDP1-DT (HGNC:26370): (CTDP1 divergent transcript)

CTDP1-DT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 18-79679637-G-T is Benign according to our data. Variant chr18-79679637-G-T is described in ClinVar as [Benign]. Clinvar id is 1249937.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTDP1	NM_004715.5 link	c.-311G>T		upstream_gene_variant		ENST00000613122.5	NP_004706.3	Q9Y5B0-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CTDP1-DT	ENST00000317008.4 link	n.109C>A	non_coding_transcript_exon_variant	Exon 1 of 5	2
CTDP1	ENST00000613122.5 link	c.-311G>T	upstream_gene_variant		1	NM_004715.5	ENSP00000484525.2	Q9Y5B0-1
CTDP1	ENST00000075430.11 link	c.-311G>T	upstream_gene_variant		1		ENSP00000075430.7	Q9Y5B0-4

Frequencies

GnomAD3 genomes

AF:

0.124

AC:

18920

AN:

151990

Hom.:

1541

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0324

Gnomad AMI

AF:

0.204

Gnomad AMR

AF:

0.0940

Gnomad ASJ

AF:

0.100

Gnomad EAS

AF:

0.116

Gnomad SAS

AF:

0.0672

Gnomad FIN

AF:

0.176

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.185

Gnomad OTH

AF:

0.110

GnomAD3 exomes

AF:

0.126

AC:

15972

AN:

127194

Hom.:

1241

AF XY:

0.125

AC XY:

8696

AN XY:

69614

show subpopulations

Gnomad AFR exome

AF:

0.0288

Gnomad AMR exome

AF:

0.0825

Gnomad ASJ exome

AF:

0.105

Gnomad EAS exome

AF:

0.122

Gnomad SAS exome

AF:

0.0734

Gnomad FIN exome

AF:

0.186

Gnomad NFE exome

AF:

0.182

Gnomad OTH exome

AF:

0.132

GnomAD4 exome

AF:

0.143

AC:

48440

AN:

339890

Hom.:

4150

Cov.:

AF XY:

0.138

AC XY:

26166

AN XY:

189706

show subpopulations

Gnomad4 AFR exome

AF:

0.0323

Gnomad4 AMR exome

AF:

0.0818

Gnomad4 ASJ exome

AF:

0.104

Gnomad4 EAS exome

AF:

0.103

Gnomad4 SAS exome

AF:

0.0753

Gnomad4 FIN exome

AF:

0.180

Gnomad4 NFE exome

AF:

0.182

Gnomad4 OTH exome

AF:

0.145

GnomAD4 genome

AF:

0.124

AC:

18913

AN:

152108

Hom.:

1540

Cov.:

AF XY:

0.121

AC XY:

9008

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.0323

Gnomad4 AMR

AF:

0.0939

Gnomad4 ASJ

AF:

0.100

Gnomad4 EAS

AF:

0.116

Gnomad4 SAS

AF:

0.0672

Gnomad4 FIN

AF:

0.176

Gnomad4 NFE

AF:

0.185

Gnomad4 OTH

AF:

0.108

Alfa

AF:

0.146

Hom.:

356

Bravo

AF:

0.115

Asia WGS

AF:

0.0850

AC:

298

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 28, 2018

GeneDx

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

-0.89

CADD

Benign

0.88

DANN

Benign

0.73

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over