chr8-67177708-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PP3BP6_Very_StrongBA1

The NM_001364869.1(CSPP1):c.3204A>G(p.Lys1068Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00271 in 1,612,298 control chromosomes in the GnomAD database, including 105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 62 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 43 hom. )

Consequence

CSPP1
NM_001364869.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.73

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

developmental delay, impaired speech, and behavioral abnormalities, with or without seizures
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Illumina, Ambry Genetics, G2P
schizophrenia
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ARFGEF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

BP6

Variant 8-67177708-A-G is Benign according to our data. Variant chr8-67177708-A-G is described in ClinVar as Benign. ClinVar VariationId is 379767.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0515 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364869.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CSPP1	NM_001382391.1	MANE Select	c.3138A>G	p.Lys1046Lys	synonymous	Exon 27 of 31	NP_001369320.1
CSPP1	NM_001364869.1		c.3204A>G	p.Lys1068Lys	synonymous	Exon 26 of 30	NP_001351798.1
CSPP1	NM_024790.7		c.3123A>G	p.Lys1041Lys	synonymous	Exon 25 of 29	NP_079066.5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CSPP1	ENST00000678616.1	MANE Select	c.3138A>G	p.Lys1046Lys	synonymous	Exon 27 of 31	ENSP00000504733.1
CSPP1	ENST00000262210.11	TSL:1	c.3204A>G	p.Lys1068Lys	synonymous	Exon 26 of 30	ENSP00000262210.6
CSPP1	ENST00000519668.1	TSL:1	c.2088A>G	p.Lys696Lys	synonymous	Exon 22 of 26	ENSP00000430092.1

Frequencies

GnomAD3 genomes

AF:

0.0151

AC:

2298

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0533

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00412

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00908

GnomAD2 exomes

AF:

0.00363

AC:

904

AN:

249370

AF XY:

0.00280

show subpopulations

Gnomad AFR exome

AF:

0.0536

Gnomad AMR exome

AF:

0.00189

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.000826

GnomAD4 exome

AF:

0.00141

AC:

2065

AN:

1459962

Hom.:

Cov.:

AF XY:

0.00123

AC XY:

894

AN XY:

726364

show subpopulations

African (AFR)

AF:

0.0523

AC:

1747

AN:

33400

American (AMR)

AF:

0.00215

AC:

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26104

East Asian (EAS)

AF:

0.00

AC:

AN:

39622

South Asian (SAS)

AF:

0.0000814

AC:

AN:

86032

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53354

Middle Eastern (MID)

AF:

0.000867

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000153

AC:

AN:

1110690

Other (OTH)

AF:

0.00320

AC:

193

AN:

60296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

175

262

350

437

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

162

216

270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0151

AC:

2306

AN:

152336

Hom.:

Cov.:

AF XY:

0.0140

AC XY:

1046

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.0533

AC:

2217

AN:

41570

American (AMR)

AF:

0.00412

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68028

Other (OTH)

AF:

0.00899

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

110

220

329

439

549

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00697

Hom.:

Bravo

AF:

0.0172

Asia WGS

AF:

0.00231

AC:

AN:

3472

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Joubert syndrome 21 (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

1.7

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.53

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.53

Position offset: 0

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over