8-67149947-CTTTTTTTTTTTTTTT-CT

Variant names:

• chr8-67149947-CTTTTTTTTTTTTTT-C
• rs11296619
• NM_001382391.1:c.2128+23_2128+36delTTTTTTTTTTTTTT

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001382391.1(CSPP1):​c.2128+23_2128+36delTTTTTTTTTTTTTT variant causes a intron change. The variant allele was found at a frequency of 0.00000439 in 1,139,168 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000011 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0000038 (0 hom.)
• Consequence: CSPP1 NM_001382391.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.17
• 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: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 8-67149947-CTTTTTTTTTTTTTT-C is Benign according to our data. Variant chr8-67149947-CTTTTTTTTTTTTTT-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1594602.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSPP1	NM_001382391.1	c.2128+23_2128+36delTTTTTTTTTTTTTT		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+23_2128+36delTTTTTTTTTTTTTT		intron_variant	Intron 18 of 30		NM_001382391.1	ENSP00000504733.1

Frequencies

GnomAD3 genomes AF: 0.0000112 AC: 1 AN: 89472 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000125

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000381 AC: 4 AN: 1049696 Hom.: 0 AF XY: 0.00000579 AC XY: 3 AN XY: 517928

African (AFR) AF: 0.00 AC: 0 AN: 22100

American (AMR) AF: 0.000111 AC: 2 AN: 17998

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15356

East Asian (EAS) AF: 0.00 AC: 0 AN: 29252

South Asian (SAS) AF: 0.00 AC: 0 AN: 43176

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36256

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3248

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 839220

Other (OTH) AF: 0.0000232 AC: 1 AN: 43090

GnomAD4 genome AF: 0.0000112 AC: 1 AN: 89472 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 41164

African (AFR) AF: 0.00 AC: 0 AN: 23092

American (AMR) AF: 0.000125 AC: 1 AN: 8032

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2460

East Asian (EAS) AF: 0.00 AC: 0 AN: 3114

South Asian (SAS) AF: 0.00 AC: 0 AN: 2532

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2940

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 158

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 45378

Other (OTH) AF: 0.00 AC: 0 AN: 1166

Alfa AF: 0.00 Hom.: 1063

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Joubert syndrome 21 Benign:1

Sep 06, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11296619; hg19: chr8-68062182;