NM_001382391.1:c.2128+25_2128+36delTTTTTTTTTTTT

Variant names:

• chr8-67149947-CTTTTTTTTTTTT-C
• rs11296619
• NM_001382391.1:c.2128+25_2128+36delTTTTTTTTTTTT

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS1

The NM_001382391.1(CSPP1):​c.2128+25_2128+36delTTTTTTTTTTTT variant causes a intron change. The variant allele was found at a frequency of 0.000127 in 1,049,692 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0018 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00013 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CSPP1 NM_001382391.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.17

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 8-67149947-CTTTTTTTTTTTT-C is Benign according to our data. Variant chr8-67149947-CTTTTTTTTTTTT-C is described in ClinVar as [Benign]. Clinvar id is 1625493.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000127 (133/1049692) while in subpopulation AFR AF= 0.00439 (97/22098). AF 95% confidence interval is 0.00368. There are 0 homozygotes in gnomad4_exome. There are 60 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSPP1	NM_001382391.1	c.2128+25_2128+36delTTTTTTTTTTTT		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+13_2128+24delTTTTTTTTTTTT		intron_variant	Intron 18 of 30		NM_001382391.1	ENSP00000504733.1

Frequencies

GnomAD3 genomes AF: 0.00178 AC: 159 AN: 89472 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00619

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00172

GnomAD4 exome AF: 0.000127 AC: 133 AN: 1049692 Hom.: 0 AF XY: 0.000116 AC XY: 60 AN XY: 517928

Gnomad4 AFR exome AF: 0.00439

Gnomad4 AMR exome AF: 0.000444

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000715

Gnomad4 OTH exome AF: 0.000464

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00178 AC: 159 AN: 89444 Hom.: 0 Cov.: 0 AF XY: 0.00209 AC XY: 86 AN XY: 41164

Gnomad4 AFR AF: 0.00619

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00171

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11296619; hg19: chr8-68062182;