8-67175475-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001382391.1(CSPP1):c.3109+39C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0075 in 1,610,576 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0051 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0077 (61 hom.)
• Consequence: CSPP1 NM_001382391.1 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.63

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]

ARFGEF1 (HGNC:15772): (ADP ribosylation factor guanine nucleotide exchange factor 1) ADP-ribosylation factors (ARFs) play an important role in intracellular vesicular trafficking. The protein encoded by this gene is involved in the activation of ARFs by accelerating replacement of bound GDP with GTP. It contains a Sec7 domain, which may be responsible for guanine-nucleotide exchange activity and also brefeldin A inhibition. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 8-67175475-C-T is Benign according to our data. Variant chr8-67175475-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1204813.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00514 (783/152280) while in subpopulation NFE AF= 0.0082 (558/68016). AF 95% confidence interval is 0.00764. There are 3 homozygotes in gnomad4. There are 354 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CSPP1	NM_001382391.1	c.3109+39C>T		intron_variant		ENST00000678616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CSPP1	ENST00000678616.1	c.3109+39C>T		intron_variant			NM_001382391.1

Frequencies

GnomAD3 genomes AF: 0.00514 AC: 782 AN: 152162 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00157

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00412

Gnomad ASJ AF: 0.0164

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.00820

Gnomad OTH AF: 0.00527

GnomAD3 exomes AF: 0.00598 AC: 1482 AN: 247788 Hom.: 14 AF XY: 0.00609 AC XY: 820 AN XY: 134572

Gnomad AFR exome AF: 0.00137

Gnomad AMR exome AF: 0.00369

Gnomad ASJ exome AF: 0.0148

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00450

Gnomad FIN exome AF: 0.000976

Gnomad NFE exome AF: 0.00867

Gnomad OTH exome AF: 0.00914

GnomAD4 exome AF: 0.00775 AC: 11298 AN: 1458296 Hom.: 61 Cov.: 29 AF XY: 0.00785 AC XY: 5693 AN XY: 725556

Gnomad4 AFR exome AF: 0.00183

Gnomad4 AMR exome AF: 0.00394

Gnomad4 ASJ exome AF: 0.0164

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00489

Gnomad4 FIN exome AF: 0.000843

Gnomad4 NFE exome AF: 0.00864

Gnomad4 OTH exome AF: 0.00755

GnomAD4 genome AF: 0.00514 AC: 783 AN: 152280 Hom.: 3 Cov.: 32 AF XY: 0.00475 AC XY: 354 AN XY: 74472

Gnomad4 AFR AF: 0.00156

Gnomad4 AMR AF: 0.00412

Gnomad4 ASJ AF: 0.0164

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00373

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00820

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.00915 Hom.: 6

Bravo AF: 0.00550

Asia WGS AF: 0.00231 AC: 8 AN: 3478

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

Jun 28, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.53
Dann	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs62513125; hg19: chr8-68087710;