Genetic Variant CSPP1:c.2128+35_2128+36delTT (chr8-67149947-CTT-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+35_2128+36delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 1,022,998 control chromosomes in the GnomAD database, including 62 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.036 ( 67 hom., cov: 0)

Exomes 𝑓: 0.24 ( 62 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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 8-67149947-CTT-C is Benign according to our data. Variant chr8-67149947-CTT-C is described in ClinVar as [Benign]. Clinvar id is 1249598.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-67149947-CTT-C is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSPP1	NM_001382391.1 link	c.2128+35_2128+36delTT		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+14delTT		intron_variant	Intron 18 of 30		NM_001382391.1	ENSP00000504733.1		A0A7I2V5W3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

3240

AN:

89574

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0190

Gnomad AMI

AF:

0.00167

Gnomad AMR

AF:

0.0269

Gnomad ASJ

AF:

0.0304

Gnomad EAS

AF:

0.00353

Gnomad SAS

AF:

0.0138

Gnomad FIN

AF:

0.0936

Gnomad MID

AF:

0.0375

Gnomad NFE

AF:

0.0475

Gnomad OTH

AF:

0.0206

GnomAD3 exomes

AF:

0.0930

AC:

6220

AN:

66916

Hom.:

AF XY:

0.0922

AC XY:

3346

AN XY:

36278

show subpopulations

Gnomad AFR exome

AF:

0.113

Gnomad AMR exome

AF:

0.140

Gnomad ASJ exome

AF:

0.111

Gnomad EAS exome

AF:

0.0990

Gnomad SAS exome

AF:

0.113

Gnomad FIN exome

AF:

0.0959

Gnomad NFE exome

AF:

0.0779

Gnomad OTH exome

AF:

0.103

GnomAD4 exome

AF:

0.243

AC:

248622

AN:

1022998

Hom.:

AF XY:

0.240

AC XY:

120961

AN XY:

504828

show subpopulations

Gnomad4 AFR exome

AF:

0.231

Gnomad4 AMR exome

AF:

0.161

Gnomad4 ASJ exome

AF:

0.228

Gnomad4 EAS exome

AF:

0.208

Gnomad4 SAS exome

AF:

0.200

Gnomad4 FIN exome

AF:

0.166

Gnomad4 NFE exome

AF:

0.252

Gnomad4 OTH exome

AF:

0.241

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0362

AC:

3240

AN:

89546

Hom.:

Cov.:

AF XY:

0.0380

AC XY:

1566

AN XY:

41216

show subpopulations

Gnomad4 AFR

AF:

0.0190

Gnomad4 AMR

AF:

0.0269

Gnomad4 ASJ

AF:

0.0304

Gnomad4 EAS

AF:

0.00355

Gnomad4 SAS

AF:

0.0143

Gnomad4 FIN

AF:

0.0936

Gnomad4 NFE

AF:

0.0475

Gnomad4 OTH

AF:

0.0205

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Joubert syndrome 21

Benign:1

Sep 25, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Sep 02, 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-CTTTTTTTTTTTTT

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