8-67175044-A-G

Position:

• chr8-67175044-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001382391.1(CSPP1):​c.2969-252A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0825 in 413,044 control chromosomes in the GnomAD database, including 3,230 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (2359 hom., cov: 31)
  • Exomes 𝑓: 0.058 (871 hom.)
• Consequence: CSPP1 NM_001382391.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.777

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 8-67175044-A-G is Benign according to our data. Variant chr8-67175044-A-G is described in ClinVar as [Benign]. Clinvar id is 1270546.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CSPP1	NM_001382391.1	c.2969-252A>G		intron_variant		ENST00000678616.1	NP_001369320.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CSPP1	ENST00000678616.1	c.2969-252A>G		intron_variant			NM_001382391.1	ENSP00000504733

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19000 AN: 151882 Hom.: 2350 Cov.: 31

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0881

Gnomad ASJ AF: 0.0481

Gnomad EAS AF: 0.0259

Gnomad SAS AF: 0.0884

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0321

Gnomad OTH AF: 0.103

GnomAD4 exome AF: 0.0576 AC: 15030 AN: 261044 Hom.: 871 Cov.: 0 AF XY: 0.0583 AC XY: 8161 AN XY: 140074

Gnomad4 AFR exome AF: 0.321

Gnomad4 AMR exome AF: 0.0885

Gnomad4 ASJ exome AF: 0.0430

Gnomad4 EAS exome AF: 0.0341

Gnomad4 SAS exome AF: 0.0833

Gnomad4 FIN exome AF: 0.107

Gnomad4 NFE exome AF: 0.0339

Gnomad4 OTH exome AF: 0.0655

GnomAD4 genome AF: 0.125 AC: 19052 AN: 152000 Hom.: 2359 Cov.: 31 AF XY: 0.128 AC XY: 9504 AN XY: 74288

Gnomad4 AFR AF: 0.319

Gnomad4 AMR AF: 0.0883

Gnomad4 ASJ AF: 0.0481

Gnomad4 EAS AF: 0.0260

Gnomad4 SAS AF: 0.0877

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.0321

Gnomad4 OTH AF: 0.102

Alfa AF: 0.0448 Hom.: 583

Bravo AF: 0.130

Asia WGS AF: 0.0740 AC: 256 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.32
DANN	Benign	0.54

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: rs2290585; hg19: chr8-68087279;