Variant 8-67175044-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.777

Variant links:

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 links:

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]

ARFGEF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
CSPP1	NM_001382391.1 linkuse as main transcript	c.2969-252A>G		intron_variant		ENST00000678616.1

Ensembl

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

Frequencies

GnomAD3 genomes

AF:

0.125

AC:

19000

AN:

151882

Hom.:

2350

Cov.:

show subpopulations

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.:

AF XY:

0.0583

AC XY:

8161

AN XY:

140074

show subpopulations

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.:

AF XY:

0.128

AC XY:

9504

AN XY:

74288

show subpopulations

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:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over