7-130434389-G-T

Variant names:

• chr7-130434389-G-T
• rs6467308
• NM_018718.3:c.34-6371C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018718.3(CEP41):​c.34-6371C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 151,964 control chromosomes in the GnomAD database, including 20,236 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (20236 hom., cov: 32)
• Consequence: CEP41 NM_018718.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP41	NM_018718.3	c.34-6371C>A		intron_variant	Intron 1 of 10	ENST00000223208.10	NP_061188.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP41	ENST00000223208.10	c.34-6371C>A		intron_variant	Intron 1 of 10	1	NM_018718.3	ENSP00000223208.4

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77927 AN: 151844 Hom.: 20197 Cov.: 32

Gnomad AFR AF: 0.572

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.514

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.513 AC: 78021 AN: 151964 Hom.: 20236 Cov.: 32 AF XY: 0.507 AC XY: 37692 AN XY: 74278

African (AFR) AF: 0.573 AC: 23751 AN: 41450

American (AMR) AF: 0.479 AC: 7321 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 1788 AN: 3470

East Asian (EAS) AF: 0.369 AC: 1909 AN: 5170

South Asian (SAS) AF: 0.494 AC: 2375 AN: 4810

European-Finnish (FIN) AF: 0.463 AC: 4884 AN: 10540

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.506 AC: 34379 AN: 67936

Other (OTH) AF: 0.517 AC: 1091 AN: 2112

Alfa AF: 0.438 Hom.: 1734

Bravo AF: 0.514

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.8
DANN	Benign	0.14
PhyloP100		0.031
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: rs6467308; hg19: chr7-130074230;