8-67149947-CTTTTTTTTTTTTTTT-CTTTTTTT

Position:

• chr8-67149947-CTTTTTTTTTTTTTTT-CTTTTTTT

Variant summary

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

The NM_001382391.1(CSPP1):​c.2128+29_2128+36delTTTTTTTT variant causes a intron change. The variant allele was found at a frequency of 0.0000799 in 1,139,054 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00012 (1 hom., cov: 0)
  • Exomes 𝑓: 0.000076 (0 hom.)
• Consequence: CSPP1 NM_001382391.1 intron
• Clinical Significance: Not reported in ClinVar
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000123 (11/89444) while in subpopulation SAS AF= 0.00238 (6/2518). AF 95% confidence interval is 0.00104. There are 1 homozygotes in gnomad4. There are 5 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+29_2128+36delTTTTTTTT		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+13_2128+20delTTTTTTTT		intron_variant			NM_001382391.1	ENSP00000504733.1

Frequencies

GnomAD3 genomes AF: 0.000123 AC: 11 AN: 89472 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.000217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00237

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000762 AC: 80 AN: 1049610 Hom.: 0 AF XY: 0.0000908 AC XY: 47 AN XY: 517882

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000651

Gnomad4 EAS exome AF: 0.0000342

Gnomad4 SAS exome AF: 0.000672

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000512

Gnomad4 OTH exome AF: 0.000139

GnomAD4 genome AF: 0.000123 AC: 11 AN: 89444 Hom.: 1 Cov.: 0 AF XY: 0.000121 AC XY: 5 AN XY: 41164

Gnomad4 AFR AF: 0.000216

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00238

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

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;