rs113941736

Positions:

chr7-130400746-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000223208.10(CEP41):c.718T>G(p.Cys240Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00132 in 1,613,780 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. C240C) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0069 ( 10 hom., cov: 32)

Exomes 𝑓: 0.00074 ( 16 hom. )

Consequence

CEP41
ENST00000223208.10 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 7.36

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 (MetaRNN=0.010561943).

BP6

Variant 7-130400746-A-C is Benign according to our data. Variant chr7-130400746-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 128705.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-130400746-A-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00693 (1056/152324) while in subpopulation AFR AF= 0.0243 (1009/41582). AF 95% confidence interval is 0.023. There are 10 homozygotes in gnomad4. There are 458 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP41	NM_018718.3 linkuse as main transcript	c.718T>G	p.Cys240Gly	missense_variant	9/11	ENST00000223208.10	NP_061188.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEP41	ENST00000223208.10 linkuse as main transcript	c.718T>G	p.Cys240Gly	missense_variant	9/11	1	NM_018718.3	ENSP00000223208	P3	Q9BYV8-1

Frequencies

GnomAD3 genomes

AF:

0.00693

AC:

1055

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00166

AC:

417

AN:

250872

Hom.:

AF XY:

0.00111

AC XY:

150

AN XY:

135558

show subpopulations

Gnomad AFR exome

AF:

0.0233

Gnomad AMR exome

AF:

0.000753

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000132

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.000738

AC:

1079

AN:

1461456

Hom.:

Cov.:

AF XY:

0.000659

AC XY:

479

AN XY:

726994

show subpopulations

Gnomad4 AFR exome

AF:

0.0278

Gnomad4 AMR exome

AF:

0.000805

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000929

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000162

Gnomad4 OTH exome

AF:

0.00132

GnomAD4 genome

AF:

0.00693

AC:

1056

AN:

152324

Hom.:

Cov.:

AF XY:

0.00615

AC XY:

458

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0243

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00614

Alfa

AF:

0.00119

Hom.:

Bravo

AF:

0.00797

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0211

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00203

AC:

247

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2023	CEP41: BS1, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Mar 10, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 18, 2018	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:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jan 08, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.65

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.27

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Benign

0.13

.;T;.

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

D;D;D

MetaRNN

Benign

0.011

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.3

.;L;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.79

PROVEAN

Pathogenic

-5.1

D;D;D

REVEL

Benign

0.28

Sift

Uncertain

0.023

D;D;D

Sift4G

Uncertain

0.0080

D;D;D

Polyphen

0.95, 0.94

.;P;P

Vest4

0.84

MVP

0.79

MPC

0.23

ClinPred

0.020

GERP RS

6.0

Varity_R

0.57

gMVP

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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