chr8-67149947-CTTTTT-C

Position:

• chr8-67149947-CTTTTT-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP6_Moderate BS1

The NM_001382391.1(CSPP1):​c.2128+32_2128+36delTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00538 in 1,129,998 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00013 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0058 (0 hom.)
• Consequence: CSPP1 NM_001382391.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.10

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 8-67149947-CTTTTT-C is Benign according to our data. Variant chr8-67149947-CTTTTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 1213678.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr8-67149947-CTTTTT-C is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000134 (12/89440) while in subpopulation SAS AF= 0.00357 (9/2518). AF 95% confidence interval is 0.00186. There are 0 homozygotes in gnomad4. There are 10 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSPP1	NM_001382391.1	c.2128+32_2128+36delTTTTT		intron_variant		ENST00000678616.1	NP_001369320.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSPP1	ENST00000678616.1	c.2128+32_2128+36delTTTTT		intron_variant			NM_001382391.1	ENSP00000504733.1

Frequencies

GnomAD3 genomes AF: 0.000134 AC: 12 AN: 89468 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00355

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00947 AC: 634 AN: 66916 Hom.: 0 AF XY: 0.0104 AC XY: 376 AN XY: 36278

Gnomad AFR exome AF: 0.00706

Gnomad AMR exome AF: 0.0103

Gnomad ASJ exome AF: 0.00811

Gnomad EAS exome AF: 0.00883

Gnomad SAS exome AF: 0.0199

Gnomad FIN exome AF: 0.0141

Gnomad NFE exome AF: 0.00763

Gnomad OTH exome AF: 0.00912

GnomAD4 exome AF: 0.00583 AC: 6068 AN: 1040558 Hom.: 0 AF XY: 0.00622 AC XY: 3190 AN XY: 513172

Gnomad4 AFR exome AF: 0.00676

Gnomad4 AMR exome AF: 0.00849

Gnomad4 ASJ exome AF: 0.00845

Gnomad4 EAS exome AF: 0.00883

Gnomad4 SAS exome AF: 0.0164

Gnomad4 FIN exome AF: 0.0107

Gnomad4 NFE exome AF: 0.00483

Gnomad4 OTH exome AF: 0.00645

GnomAD4 genome AF: 0.000134 AC: 12 AN: 89440 Hom.: 0 Cov.: 0 AF XY: 0.000243 AC XY: 10 AN XY: 41160

Gnomad4 AFR AF: 0.000130

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00357

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 01, 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: rs11296619; hg19: chr8-68062182;