Genetic Variant CEP41:c.575-14delT (chr7-130401961-GA-G) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_018718.3(CEP41):c.575-14delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0153 in 1,594,694 control chromosomes in the GnomAD database, including 243 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 17 hom., cov: 31)

Exomes 𝑓: 0.016 ( 226 hom. )

Consequence

CEP41
NM_018718.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.18

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 7-130401961-GA-G is Benign according to our data. Variant chr7-130401961-GA-G is described in ClinVar as [Benign]. Clinvar id is 261055.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-130401961-GA-G is described in Lovd as [Benign]. Variant chr7-130401961-GA-G is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0128 (1952/152286) while in subpopulation NFE AF= 0.0194 (1319/68024). AF 95% confidence interval is 0.0185. There are 17 homozygotes in gnomad4. There are 991 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 17 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP41	NM_018718.3 link	c.575-14delT		intron_variant	Intron 7 of 10	ENST00000223208.10	NP_061188.1	Q9BYV8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP41	ENST00000223208.10 link	c.575-14delT		intron_variant	Intron 7 of 10	1	NM_018718.3	ENSP00000223208.4		Q9BYV8-1

Frequencies

GnomAD3 genomes

AF:

0.0128

AC:

1954

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00319

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00596

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00725

Gnomad FIN

AF:

0.0327

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0194

Gnomad OTH

AF:

0.00766

GnomAD3 exomes

AF:

0.0132

AC:

3310

AN:

251318

Hom.:

AF XY:

0.0134

AC XY:

1823

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.00271

Gnomad AMR exome

AF:

0.00448

Gnomad ASJ exome

AF:

0.00367

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00827

Gnomad FIN exome

AF:

0.0315

Gnomad NFE exome

AF:

0.0180

Gnomad OTH exome

AF:

0.0162

GnomAD4 exome

AF:

0.0156

AC:

22497

AN:

1442408

Hom.:

226

Cov.:

AF XY:

0.0157

AC XY:

11293

AN XY:

718582

show subpopulations

Gnomad4 AFR exome

AF:

0.00194

Gnomad4 AMR exome

AF:

0.00472

Gnomad4 ASJ exome

AF:

0.00400

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.00831

Gnomad4 FIN exome

AF:

0.0315

Gnomad4 NFE exome

AF:

0.0173

Gnomad4 OTH exome

AF:

0.0126

GnomAD4 genome

AF:

0.0128

AC:

1952

AN:

152286

Hom.:

Cov.:

AF XY:

0.0133

AC XY:

991

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00318

Gnomad4 AMR

AF:

0.00595

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00726

Gnomad4 FIN

AF:

0.0327

Gnomad4 NFE

AF:

0.0194

Gnomad4 OTH

AF:

0.00710

Bravo

AF:

0.00962

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Apr 07, 2016

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Apr 20, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Joubert syndrome 15

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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.

7-130401961-GAA-GA

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