rs528357182

chr8-67158977-TTTTTA-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS1

The NM_001382391.1(CSPP1):c.2392-8_2392-4del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000533 in 1,582,104 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00082 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00050 (3 hom.)
• Consequence: CSPP1 NM_001382391.1 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.560

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 Benign. Variant got -12 ACMG points.

• BP6: Variant 8-67158977-TTTTTA-T is Benign according to our data. Variant chr8-67158977-TTTTTA-T is described in ClinVar as [Likely_benign]. Clinvar id is 372673.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-67158977-TTTTTA-T is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000821 (125/152308) while in subpopulation AMR AF= 0.00261 (40/15308). AF 95% confidence interval is 0.00197. There are 0 homozygotes in gnomad4. There are 77 alleles in male gnomad4 subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSPP1	NM_001382391.1	c.2392-8_2392-4del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000678616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSPP1	ENST00000678616.1	c.2392-8_2392-4del		splice_polypyrimidine_tract_variant, intron_variant			NM_001382391.1

Frequencies

GnomAD3 genomes AF: 0.000815 AC: 124 AN: 152190 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00192

GnomAD3 exomes AF: 0.000875 AC: 199 AN: 227374 Hom.: 1 AF XY: 0.000888 AC XY: 110 AN XY: 123890

Gnomad AFR exome AF: 0.000134

Gnomad AMR exome AF: 0.00102

Gnomad ASJ exome AF: 0.0119

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000384

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000437

Gnomad OTH exome AF: 0.00110

GnomAD4 exome AF: 0.000502 AC: 718 AN: 1429796 Hom.: 3 AF XY: 0.000521 AC XY: 371 AN XY: 711562

Gnomad4 AFR exome AF: 0.000735

Gnomad4 AMR exome AF: 0.000905

Gnomad4 ASJ exome AF: 0.0124

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000346

Gnomad4 FIN exome AF: 0.0000189

Gnomad4 NFE exome AF: 0.000200

Gnomad4 OTH exome AF: 0.00127

GnomAD4 genome AF: 0.000821 AC: 125 AN: 152308 Hom.: 0 Cov.: 32 AF XY: 0.00103 AC XY: 77 AN XY: 74478

Gnomad4 AFR AF: 0.000217

Gnomad4 AMR AF: 0.00261

Gnomad4 ASJ AF: 0.0141

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000828

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.00196 Hom.: 1

Bravo AF: 0.000759

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2017	- -

Joubert syndrome 21 Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 19, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Al Jalila Children's Genomics Center, Al Jalila Childrens Speciality Hospital	Mar 25, 2020	- -

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: rs528357182; hg19: chr8-68071212;