Genetic Variant CSPP1:c.2128+34_2128+36delTTT (chr8-67149947-CTTT-C) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001382391.1(CSPP1):c.2128+34_2128+36delTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 989,022 control chromosomes in the GnomAD database, including 6 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 31 hom., cov: 0)

Exomes 𝑓: 0.12 ( 6 hom. )

Failed GnomAD Quality Control

Consequence

CSPP1
NM_001382391.1 intron

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 0.0650

Variant links:

Genes affected

CSPP1 (HGNC:26193): (centrosome and spindle pole associated protein 1) This gene encodes a centrosome and spindle pole associated protein. The encoded protein plays a role in cell-cycle progression and spindle organization, regulates cytokinesis, interacts with Nephrocystin 8 and is required for cilia formation. Mutations in this gene result in primary cilia abnormalities and classical Joubert syndrome. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Apr 2014]

CSPP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 8-67149947-CTTT-C is Benign according to our data. Variant chr8-67149947-CTTT-C is described in ClinVar as [Benign]. Clinvar id is 1277073.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-67149947-CTTT-C is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSPP1	NM_001382391.1 link	c.2128+34_2128+36delTTT		intron_variant	Intron 18 of 30	ENST00000678616.1	NP_001369320.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSPP1	ENST00000678616.1 link	c.2128+13_2128+15delTTT		intron_variant	Intron 18 of 30		NM_001382391.1	ENSP00000504733.1		A0A7I2V5W3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

1732

AN:

89468

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0351

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0139

Gnomad ASJ

AF:

0.00773

Gnomad EAS

AF:

0.0193

Gnomad SAS

AF:

0.0300

Gnomad FIN

AF:

0.110

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.00668

Gnomad OTH

AF:

0.0180

GnomAD3 exomes

AF:

0.0658

AC:

4402

AN:

66916

Hom.:

AF XY:

0.0673

AC XY:

2441

AN XY:

36278

show subpopulations

Gnomad AFR exome

AF:

0.0739

Gnomad AMR exome

AF:

0.106

Gnomad ASJ exome

AF:

0.0637

Gnomad EAS exome

AF:

0.0762

Gnomad SAS exome

AF:

0.0735

Gnomad FIN exome

AF:

0.0739

Gnomad NFE exome

AF:

0.0549

Gnomad OTH exome

AF:

0.0701

GnomAD4 exome

AF:

0.119

AC:

117995

AN:

989022

Hom.:

AF XY:

0.120

AC XY:

58627

AN XY:

487730

show subpopulations

Gnomad4 AFR exome

AF:

0.124

Gnomad4 AMR exome

AF:

0.116

Gnomad4 ASJ exome

AF:

0.136

Gnomad4 EAS exome

AF:

0.134

Gnomad4 SAS exome

AF:

0.125

Gnomad4 FIN exome

AF:

0.123

Gnomad4 NFE exome

AF:

0.118

Gnomad4 OTH exome

AF:

0.126

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0193

AC:

1727

AN:

89440

Hom.:

Cov.:

AF XY:

0.0228

AC XY:

938

AN XY:

41154

show subpopulations

Gnomad4 AFR

AF:

0.0350

Gnomad4 AMR

AF:

0.0138

Gnomad4 ASJ

AF:

0.00773

Gnomad4 EAS

AF:

0.0191

Gnomad4 SAS

AF:

0.0298

Gnomad4 FIN

AF:

0.110

Gnomad4 NFE

AF:

0.00668

Gnomad4 OTH

AF:

0.0179

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Joubert syndrome 21

Benign:1

Nov 07, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Aug 18, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Publications

LitVar

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

8-67149947-CTTTTTTTTTTTTTTT-CTTTTTTTTTTTT

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