Variant 7-130394596-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_018718.3(CEP41):c.*4295G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 453,184 control chromosomes in the GnomAD database, including 27,615 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10260 hom., cov: 31)

Exomes 𝑓: 0.33 ( 17355 hom. )

Consequence

CEP41
NM_018718.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.909

Variant links:

Genes affected

CEP41 (HGNC:12370): (centrosomal protein 41) This gene encodes a centrosomal and microtubule-binding protein which is predicted to have two coiled-coil domains and a rhodanese domain. In human retinal pigment epithelial cells the protein localized to centrioles and cilia. Mutations in this gene have been associated with Joubert Syndrome 15; an autosomal recessive ciliopathy and neurological disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2012]

CEP41 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 7-130394596-C-G is Benign according to our data. Variant chr7-130394596-C-G is described in ClinVar as [Benign]. Clinvar id is 358896.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP41	NM_018718.3 linkuse as main transcript	c.*4295G>C		3_prime_UTR_variant	11/11	ENST00000223208.10	NP_061188.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP41	ENST00000223208.10 linkuse as main transcript	c.*4295G>C	3_prime_UTR_variant	11/11	1	NM_018718.3	ENSP00000223208	P3	Q9BYV8-1
CEP41	ENST00000541543.6 linkuse as main transcript	c.*4295G>C	3_prime_UTR_variant	11/11	2		ENSP00000445888
CEP41	ENST00000675649.1 linkuse as main transcript	c.*4295G>C	3_prime_UTR_variant	9/9			ENSP00000502385

Frequencies

GnomAD3 genomes

AF:

0.361

AC:

54866

AN:

151798

Hom.:

10256

Cov.:

show subpopulations

Gnomad AFR

AF:

0.446

Gnomad AMI

AF:

0.260

Gnomad AMR

AF:

0.311

Gnomad ASJ

AF:

0.390

Gnomad EAS

AF:

0.230

Gnomad SAS

AF:

0.314

Gnomad FIN

AF:

0.321

Gnomad MID

AF:

0.437

Gnomad NFE

AF:

0.341

Gnomad OTH

AF:

0.365

GnomAD3 exomes

AF:

0.323

AC:

41236

AN:

127810

Hom.:

6897

AF XY:

0.324

AC XY:

22688

AN XY:

69996

show subpopulations

Gnomad AFR exome

AF:

0.452

Gnomad AMR exome

AF:

0.263

Gnomad ASJ exome

AF:

0.389

Gnomad EAS exome

AF:

0.247

Gnomad SAS exome

AF:

0.319

Gnomad FIN exome

AF:

0.328

Gnomad NFE exome

AF:

0.341

Gnomad OTH exome

AF:

0.349

GnomAD4 exome

AF:

0.334

AC:

100701

AN:

301268

Hom.:

17355

Cov.:

AF XY:

0.333

AC XY:

57242

AN XY:

171646

show subpopulations

Gnomad4 AFR exome

AF:

0.437

Gnomad4 AMR exome

AF:

0.263

Gnomad4 ASJ exome

AF:

0.388

Gnomad4 EAS exome

AF:

0.238

Gnomad4 SAS exome

AF:

0.322

Gnomad4 FIN exome

AF:

0.340

Gnomad4 NFE exome

AF:

0.345

Gnomad4 OTH exome

AF:

0.344

GnomAD4 genome

AF:

0.361

AC:

54897

AN:

151916

Hom.:

10260

Cov.:

AF XY:

0.356

AC XY:

26428

AN XY:

74236

show subpopulations

Gnomad4 AFR

AF:

0.445

Gnomad4 AMR

AF:

0.310

Gnomad4 ASJ

AF:

0.390

Gnomad4 EAS

AF:

0.231

Gnomad4 SAS

AF:

0.313

Gnomad4 FIN

AF:

0.321

Gnomad4 NFE

AF:

0.341

Gnomad4 OTH

AF:

0.365

Alfa

AF:

0.287

Hom.:

1193

Bravo

AF:

0.362

Asia WGS

AF:

0.229

AC:

797

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Joubert syndrome 15

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

DANN

Benign

0.60

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