7-130401961-GAA-GA

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

Joubert syndrome 15
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
Joubert syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Joubert syndrome with ocular defect
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CEP41 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 261055.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 17 AR 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

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

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

GnomAD2 exomes

AF:

0.0132

AC:

3310

AN:

251318

AF XY:

0.0134

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 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

African (AFR)

AF:

0.00194

AC:

AN:

33060

American (AMR)

AF:

0.00472

AC:

211

AN:

44670

Ashkenazi Jewish (ASJ)

AF:

0.00400

AC:

104

AN:

26000

East Asian (EAS)

AF:

0.0000505

AC:

AN:

39572

South Asian (SAS)

AF:

0.00831

AC:

714

AN:

85870

European-Finnish (FIN)

AF:

0.0315

AC:

1678

AN:

53310

Middle Eastern (MID)

AF:

0.00261

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.0173

AC:

18958

AN:

1094502

Other (OTH)

AF:

0.0126

AC:

751

AN:

59684

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

975

1949

2924

3898

4873

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

672

1344

2016

2688

3360

<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:

0.0128

AC:

1952

AN:

152286

Hom.:

Cov.:

AF XY:

0.0133

AC XY:

991

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.00318

AC:

132

AN:

41566

American (AMR)

AF:

0.00595

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00259

AC:

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5186

South Asian (SAS)

AF:

0.00726

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0327

AC:

347

AN:

10598

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0194

AC:

1319

AN:

68024

Other (OTH)

AF:

0.00710

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

197

296

394

493

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.0114

Hom.:

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

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Apr 07, 2016

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

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

PhyloP100

1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over