NM_001382391.1:c.2128+30_2128+36delTTTTTTT

Variant names:

• chr8-67149947-CTTTTTTT-C
• rs11296619
• NM_001382391.1:c.2128+30_2128+36delTTTTTTT

Variant summary

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

The NM_001382391.1(CSPP1):​c.2128+30_2128+36delTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000154 in 1,138,726 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000011 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00017 (0 hom.)
• Consequence: CSPP1 NM_001382391.1 intron
• Clinical Significance: Not reported in ClinVar
• 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]

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_exome allele frequency = 0.000166 (174/1049254) while in subpopulation SAS AF= 0.00111 (48/43146). AF 95% confidence interval is 0.000862. There are 0 homozygotes in gnomad4_exome. There are 100 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+30_2128+36delTTTTTTT		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+19delTTTTTTT		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: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000321

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: 0.000166 AC: 174 AN: 1049254 Hom.: 0 AF XY: 0.000193 AC XY: 100 AN XY: 517710

Gnomad4 AFR exome AF: 0.0000905

Gnomad4 AMR exome AF: 0.000278

Gnomad4 ASJ exome AF: 0.000130

Gnomad4 EAS exome AF: 0.000376

Gnomad4 SAS exome AF: 0.00111

Gnomad4 FIN exome AF: 0.000193

Gnomad4 NFE exome AF: 0.000110

Gnomad4 OTH exome AF: 0.000163

GnomAD4 genome AF: 0.0000112 AC: 1 AN: 89472 Hom.: 0 Cov.: 0 AF XY: 0.0000243 AC XY: 1 AN XY: 41164

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000321

Gnomad4 SAS AF: 0.00

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;