18-79679532-T-C

Variant summary

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

The XM_047437922.1(CTDP1):ā€‹c.131T>Cā€‹(p.Leu44Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 458,636 control chromosomes in the GnomAD database, including 92,442 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 (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.64 ( 31094 hom., cov: 32)
Exomes š‘“: 0.63 ( 61348 hom. )

Consequence

CTDP1
XM_047437922.1 missense

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -6.87
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.99).
BP6
Variant 18-79679532-T-C is Benign according to our data. Variant chr18-79679532-T-C is described in ClinVar as [Benign]. Clinvar id is 1278218.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CTDP1XM_047437922.1 linkuse as main transcriptc.131T>C p.Leu44Pro missense_variant 1/13 XP_047293878.1
CTDP1XM_047437926.1 linkuse as main transcriptc.50T>C p.Leu17Pro missense_variant 1/12 XP_047293882.1
CTDP1XM_047437924.1 linkuse as main transcriptc.-44+302T>C intron_variant XP_047293880.1
CTDP1-DTNR_136643.1 linkuse as main transcriptn.214A>G non_coding_transcript_exon_variant 1/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CTDP1-DTENST00000317008.4 linkuse as main transcriptn.214A>G non_coding_transcript_exon_variant 1/52

Frequencies

GnomAD3 genomes
AF:
0.638
AC:
96749
AN:
151756
Hom.:
31061
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.676
Gnomad AMI
AF:
0.659
Gnomad AMR
AF:
0.649
Gnomad ASJ
AF:
0.661
Gnomad EAS
AF:
0.580
Gnomad SAS
AF:
0.711
Gnomad FIN
AF:
0.697
Gnomad MID
AF:
0.712
Gnomad NFE
AF:
0.599
Gnomad OTH
AF:
0.649
GnomAD3 exomes
AF:
0.635
AC:
81503
AN:
128372
Hom.:
26029
AF XY:
0.636
AC XY:
44700
AN XY:
70302
show subpopulations
Gnomad AFR exome
AF:
0.678
Gnomad AMR exome
AF:
0.643
Gnomad ASJ exome
AF:
0.656
Gnomad EAS exome
AF:
0.575
Gnomad SAS exome
AF:
0.701
Gnomad FIN exome
AF:
0.687
Gnomad NFE exome
AF:
0.599
Gnomad OTH exome
AF:
0.625
GnomAD4 exome
AF:
0.630
AC:
193229
AN:
306762
Hom.:
61348
Cov.:
0
AF XY:
0.636
AC XY:
110939
AN XY:
174450
show subpopulations
Gnomad4 AFR exome
AF:
0.674
Gnomad4 AMR exome
AF:
0.643
Gnomad4 ASJ exome
AF:
0.655
Gnomad4 EAS exome
AF:
0.576
Gnomad4 SAS exome
AF:
0.701
Gnomad4 FIN exome
AF:
0.680
Gnomad4 NFE exome
AF:
0.596
Gnomad4 OTH exome
AF:
0.625
GnomAD4 genome
AF:
0.638
AC:
96832
AN:
151874
Hom.:
31094
Cov.:
32
AF XY:
0.645
AC XY:
47869
AN XY:
74254
show subpopulations
Gnomad4 AFR
AF:
0.677
Gnomad4 AMR
AF:
0.649
Gnomad4 ASJ
AF:
0.661
Gnomad4 EAS
AF:
0.579
Gnomad4 SAS
AF:
0.710
Gnomad4 FIN
AF:
0.697
Gnomad4 NFE
AF:
0.599
Gnomad4 OTH
AF:
0.647
Alfa
AF:
0.621
Hom.:
8379
Bravo
AF:
0.632
Asia WGS
AF:
0.669
AC:
2327
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
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingGeneDxJun 29, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.99
CADD
Benign
2.7
DANN
Benign
0.70

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.

Other links and lift over

dbSNP: rs3826573; hg19: chr18-77439532; COSMIC: COSV50008198; API