rs140627086

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_004715.5(CTDP1):c.2274G>A(p.Pro758Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00509 in 1,613,568 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0029 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0053 ( 26 hom. )

Consequence

CTDP1
NM_004715.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -1.57

Publications

1 publications found

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 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)

CTDP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

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

BP6

Variant 18-79717873-G-A is Benign according to our data. Variant chr18-79717873-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 210803.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.58 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTDP1	NM_004715.5 link	c.2274G>A	p.Pro758Pro	synonymous_variant	Exon 10 of 13	ENST00000613122.5	NP_004706.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
CTDP1	ENST00000613122.5 link	c.2274G>A	p.Pro758Pro	synonymous_variant	Exon 10 of 13	1	NM_004715.5	ENSP00000484525.2
CTDP1	ENST00000075430.11 link	c.2274G>A	p.Pro758Pro	synonymous_variant	Exon 10 of 12	1		ENSP00000075430.7
CTDP1	ENST00000591598.5 link	c.2070G>A	p.Pro690Pro	synonymous_variant	Exon 10 of 12	1		ENSP00000465119.1
CTDP1	ENST00000299543.9 link	c.894G>A	p.Pro298Pro	synonymous_variant	Exon 3 of 4	5		ENSP00000299543.9

Frequencies

GnomAD3 genomes

AF:

0.00288

AC:

438

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000989

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.00273

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00451

Gnomad OTH

AF:

0.00383

GnomAD2 exomes

AF:

0.00325

AC:

815

AN:

250840

AF XY:

0.00328

show subpopulations

Gnomad AFR exome

AF:

0.00118

Gnomad AMR exome

AF:

0.00185

Gnomad ASJ exome

AF:

0.00238

Gnomad EAS exome

AF:

0.000272

Gnomad FIN exome

AF:

0.00363

Gnomad NFE exome

AF:

0.00474

Gnomad OTH exome

AF:

0.00360

GnomAD4 exome

AF:

0.00531

AC:

7765

AN:

1461266

Hom.:

Cov.:

AF XY:

0.00519

AC XY:

3772

AN XY:

726976

show subpopulations

African (AFR)

AF:

0.000956

AC:

AN:

33478

American (AMR)

AF:

0.00152

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00176

AC:

AN:

26130

East Asian (EAS)

AF:

0.000101

AC:

AN:

39696

South Asian (SAS)

AF:

0.00250

AC:

216

AN:

86258

European-Finnish (FIN)

AF:

0.00337

AC:

178

AN:

52858

Middle Eastern (MID)

AF:

0.00173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00623

AC:

6927

AN:

1111970

Other (OTH)

AF:

0.00470

AC:

284

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

540

1080

1620

2160

2700

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

266

532

798

1064

1330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00289

AC:

440

AN:

152302

Hom.:

Cov.:

AF XY:

0.00263

AC XY:

196

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.000986

AC:

AN:

41578

American (AMR)

AF:

0.00222

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5172

South Asian (SAS)

AF:

0.00269

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00273

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00451

AC:

307

AN:

68012

Other (OTH)

AF:

0.00379

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

106

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00370

Hom.:

Bravo

AF:

0.00312

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00442

EpiControl

AF:

0.00445

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided