7-130393789-C-T

Variant names:

• chr7-130393789-C-T
• rs1990790
• NM_018718.3:c.*5102G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.53
• Publications: 21 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 358883.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
CEP41	NM_018718.3	c.*5102G>A		3_prime_UTR_variant	Exon 11 of 11	ENST00000223208.10	NP_061188.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP41	ENST00000223208.10	c.*5102G>A		3_prime_UTR_variant	Exon 11 of 11	1	NM_018718.3	ENSP00000223208.4
CEP41	ENST00000541543.6	c.*5102G>A		3_prime_UTR_variant	Exon 11 of 11	2		ENSP00000445888.2
CEP41	ENST00000675649.1	c.*5102G>A		3_prime_UTR_variant	Exon 9 of 9			ENSP00000502385.1

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

GnomAD2 exomes AF: 0.509 AC: 64518 AN: 126670 AF XY: 0.511

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 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

African (AFR) AF: 0.634 AC: 5291 AN: 8340

American (AMR) AF: 0.472 AC: 12694 AN: 26906

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 5791 AN: 10680

East Asian (EAS) AF: 0.499 AC: 4582 AN: 9188

South Asian (SAS) AF: 0.521 AC: 30926 AN: 59334

European-Finnish (FIN) AF: 0.498 AC: 6133 AN: 12320

Middle Eastern (MID) AF: 0.554 AC: 633 AN: 1142

European-Non Finnish (NFE) AF: 0.503 AC: 79305 AN: 157570

Other (OTH) AF: 0.521 AC: 7245 AN: 13906

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

African (AFR) AF: 0.632 AC: 26190 AN: 41470

American (AMR) AF: 0.496 AC: 7580 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1912 AN: 3470

East Asian (EAS) AF: 0.496 AC: 2568 AN: 5174

South Asian (SAS) AF: 0.512 AC: 2468 AN: 4822

European-Finnish (FIN) AF: 0.493 AC: 5188 AN: 10528

Middle Eastern (MID) AF: 0.497 AC: 145 AN: 292

European-Non Finnish (NFE) AF: 0.501 AC: 34052 AN: 67988

Other (OTH) AF: 0.526 AC: 1110 AN: 2110

Alfa AF: 0.512 Hom.: 30086

Bravo AF: 0.542

Asia WGS AF: 0.510 AC: 1771 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Joubert syndrome 15 Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0060
DANN	Benign	0.45
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1990790; hg19: chr7-130033630;