Variant 7-130394296-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1

The NM_018718.3(CEP41):c.*4595G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000694 in 454,056 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00068 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00070 ( 1 hom. )

Consequence

CEP41
NM_018718.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.96

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 -8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 7-130394296-C-T is Benign according to our data. Variant chr7-130394296-C-T is described in ClinVar as [Benign]. Clinvar id is 912135.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000683 (104/152262) while in subpopulation EAS AF= 0.0191 (99/5180). AF 95% confidence interval is 0.0161. There are 0 homozygotes in gnomad4. There are 53 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEP41	NM_018718.3 linkuse as main transcript	c.*4595G>A		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.*4595G>A	3_prime_UTR_variant	11/11	1	NM_018718.3	ENSP00000223208	P3	Q9BYV8-1
CEP41	ENST00000541543.6 linkuse as main transcript	c.*4595G>A	3_prime_UTR_variant	11/11	2		ENSP00000445888
CEP41	ENST00000675649.1 linkuse as main transcript	c.*4595G>A	3_prime_UTR_variant	9/9			ENSP00000502385

Frequencies

GnomAD3 genomes

AF:

0.000690

AC:

105

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00165

AC:

211

AN:

128030

Hom.:

AF XY:

0.00160

AC XY:

112

AN XY:

70114

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000411

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0196

Gnomad SAS exome

AF:

0.000134

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000211

Gnomad OTH exome

AF:

0.000501

GnomAD4 exome

AF:

0.000699

AC:

211

AN:

301794

Hom.:

Cov.:

AF XY:

0.000680

AC XY:

117

AN XY:

171996

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000367

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0212

Gnomad4 SAS exome

AF:

0.000101

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.000499

GnomAD4 genome

AF:

0.000683

AC:

104

AN:

152262

Hom.:

Cov.:

AF XY:

0.000712

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0191

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000342

Hom.:

Bravo

AF:

0.000676

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Joubert syndrome 15

Benign:1

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). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.016

DANN

Benign

0.70

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