8-67149947-CTTTTTTTTTTTTTTT-CTTTTTTTTTTTTTT

Variant names:

• chr8-67149947-CT-C
• rs11296619
• NM_001382391.1:c.2128+36delT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001382391.1(CSPP1):​c.2128+36delT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.85 (32231 hom., cov: 0)
  • Exomes 𝑓: 0.36 (902 hom.)
  • Failed GnomAD Quality Control
• Consequence: CSPP1 NM_001382391.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.26
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Joubert syndrome 21

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P
• Joubert syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Joubert syndrome with Jeune asphyxiating thoracic dystrophy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Meckel syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 8-67149947-CT-C is Benign according to our data. Variant chr8-67149947-CT-C is described in ClinVar as Benign. ClinVar VariationId is 402568.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSPP1	NM_001382391.1	c.2128+36delT		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	c.2128+36delT		intron_variant	Intron 18 of 30		NM_001382391.1	ENSP00000504733.1

Frequencies

GnomAD3 genomes AF: 0.852 AC: 76325 AN: 89560 Hom.: 32244 Cov.: 0

Gnomad AFR AF: 0.865

Gnomad AMI AF: 0.902

Gnomad AMR AF: 0.841

Gnomad ASJ AF: 0.870

Gnomad EAS AF: 0.768

Gnomad SAS AF: 0.857

Gnomad FIN AF: 0.707

Gnomad MID AF: 0.844

Gnomad NFE AF: 0.861

Gnomad OTH AF: 0.856

GnomAD2 exomes AF: 0.0590 AC: 3945 AN: 66916 AF XY: 0.0560

Gnomad AFR exome AF: 0.0603

Gnomad AMR exome AF: 0.102

Gnomad ASJ exome AF: 0.0898

Gnomad EAS exome AF: 0.0770

Gnomad FIN exome AF: 0.0598

Gnomad NFE exome AF: 0.0461

Gnomad OTH exome AF: 0.0842

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.361 AC: 372791 AN: 1032604 Hom.: 902 Cov.: 0 AF XY: 0.355 AC XY: 180785 AN XY: 509386

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.352 AC: 7627 AN: 21656

American (AMR) AF: 0.203 AC: 3604 AN: 17730

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 5002 AN: 15024

East Asian (EAS) AF: 0.301 AC: 8585 AN: 28484

South Asian (SAS) AF: 0.270 AC: 11431 AN: 42300

European-Finnish (FIN) AF: 0.210 AC: 7408 AN: 35336

Middle Eastern (MID) AF: 0.328 AC: 1042 AN: 3172

European-Non Finnish (NFE) AF: 0.379 AC: 312961 AN: 826602

Other (OTH) AF: 0.358 AC: 15131 AN: 42300

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.852 AC: 76296 AN: 89530 Hom.: 32231 Cov.: 0 AF XY: 0.844 AC XY: 34758 AN XY: 41204

African (AFR) AF: 0.865 AC: 19967 AN: 23092

American (AMR) AF: 0.841 AC: 6763 AN: 8040

Ashkenazi Jewish (ASJ) AF: 0.870 AC: 2148 AN: 2468

East Asian (EAS) AF: 0.768 AC: 2385 AN: 3106

South Asian (SAS) AF: 0.856 AC: 2153 AN: 2514

European-Finnish (FIN) AF: 0.707 AC: 2073 AN: 2932

Middle Eastern (MID) AF: 0.840 AC: 121 AN: 144

European-Non Finnish (NFE) AF: 0.861 AC: 39141 AN: 45462

Other (OTH) AF: 0.856 AC: 1002 AN: 1170

Alfa AF: 0.620 Hom.: 1063

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Joubert syndrome 21 Benign:1

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

May 17, 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
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11296619; hg19: chr8-68062182;