chr7-130434389-G-C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018718.3(CEP41):​c.34-6371C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018718.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP41	NM_018718.3	MANE Select	c.34-6371C>G		intron	N/A	NP_061188.1
	CEP41	NM_001257158.2		c.34-6371C>G		intron	N/A	NP_001244087.1
	CEP41	NM_001257159.2		c.34-6371C>G		intron	N/A	NP_001244088.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP41	ENST00000223208.10	TSL:1 MANE Select	c.34-6371C>G		intron	N/A	ENSP00000223208.4
	CEP41	ENST00000343969.10	TSL:1	c.34-6371C>G		intron	N/A	ENSP00000342738.6
	CEP41	ENST00000489512.5	TSL:1	c.34-6371C>G		intron	N/A	ENSP00000417815.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.8
DANN	Benign	0.073
PhyloP100		0.031

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;