7-130393789-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_018718.3(CEP41):c.*5102G>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 0.519 in 451,426 control chromosomes in the GnomAD database, including 61,491 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.54 (22332 hom., cov: 32)
  • Exomes 𝑓: 0.51 (39159 hom.)
• Consequence: CEP41 NM_018718.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.53

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 7-130393789-C-T is Benign according to our data. Variant chr7-130393789-C-T is described in ClinVar as [Benign]. Clinvar id is 358883.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEP41	NM_018718.3	c.*5102G>A		3_prime_UTR_variant	11/11	ENST00000223208.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEP41	ENST00000223208.10	c.*5102G>A		3_prime_UTR_variant	11/11	1	NM_018718.3	P3
CEP41	ENST00000541543.6	c.*5102G>A		3_prime_UTR_variant	11/11	2
CEP41	ENST00000675649.1	c.*5102G>A		3_prime_UTR_variant	9/9

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81707 AN: 151922 Hom.: 22294 Cov.: 32

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.523

GnomAD3 exomes AF: 0.509 AC: 64518 AN: 126670 Hom.: 16516 AF XY: 0.511 AC XY: 35428 AN XY: 69354

Gnomad AFR exome AF: 0.636

Gnomad AMR exome AF: 0.470

Gnomad ASJ exome AF: 0.545

Gnomad EAS exome AF: 0.492

Gnomad SAS exome AF: 0.519

Gnomad FIN exome AF: 0.499

Gnomad NFE exome AF: 0.506

Gnomad OTH exome AF: 0.521

GnomAD4 exome AF: 0.510 AC: 152600 AN: 299386 Hom.: 39159 Cov.: 0 AF XY: 0.511 AC XY: 87160 AN XY: 170602

Gnomad4 AFR exome AF: 0.634

Gnomad4 AMR exome AF: 0.472

Gnomad4 ASJ exome AF: 0.542

Gnomad4 EAS exome AF: 0.499

Gnomad4 SAS exome AF: 0.521

Gnomad4 FIN exome AF: 0.498

Gnomad4 NFE exome AF: 0.503

Gnomad4 OTH exome AF: 0.521

GnomAD4 genome AF: 0.538 AC: 81805 AN: 152040 Hom.: 22332 Cov.: 32 AF XY: 0.535 AC XY: 39748 AN XY: 74280

Gnomad4 AFR AF: 0.632

Gnomad4 AMR AF: 0.496

Gnomad4 ASJ AF: 0.551

Gnomad4 EAS AF: 0.496

Gnomad4 SAS AF: 0.512

Gnomad4 FIN AF: 0.493

Gnomad4 NFE AF: 0.501

Gnomad4 OTH AF: 0.526

Alfa AF: 0.508 Hom.: 22592

Bravo AF: 0.542

Asia WGS AF: 0.510 AC: 1771 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Joubert syndrome 15 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.0060
Dann	Benign	0.45

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

Other links and lift over

dbSNP: rs1990790; hg19: chr7-130033630;