rs4728195

Variant names:

• chr7-130394596-C-A
• rs4728195
• NM_018718.3:c.*4295G>T

Your query was ambiguous. Multiple possible variants found:

• chr7-130394596-C-A
• chr7-130394596-C-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.*4295G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000332 in 301,292 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 31)
  • Exomes 𝑓: 0.0000033 (0 hom.)
• Consequence: CEP41 NM_018718.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.909
• Publications: 3 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: G2P, Labcorp Genetics (formerly Invitae)
• 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=-0.75).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP41	NM_018718.3	MANE Select	c.*4295G>T		3_prime_UTR	Exon 11 of 11	NP_061188.1	Q9BYV8-1
	CEP41	NM_001257158.2		c.*4295G>T		3_prime_UTR	Exon 10 of 10	NP_001244087.1	Q9BYV8-2
	CEP41	NM_001257159.2		c.*4295G>T		3_prime_UTR	Exon 9 of 9	NP_001244088.1	Q9BYV8-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP41	ENST00000223208.10	TSL:1 MANE Select	c.*4295G>T		3_prime_UTR	Exon 11 of 11	ENSP00000223208.4	Q9BYV8-1
	CEP41	ENST00000541543.6	TSL:2	c.*4295G>T		3_prime_UTR	Exon 11 of 11	ENSP00000445888.2	A0A7I2SYM4
	CEP41	ENST00000675649.1		c.*4295G>T		3_prime_UTR	Exon 9 of 9	ENSP00000502385.1	A0A6Q8PGR4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000782 AC: 1 AN: 127810 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000411

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000332 AC: 1 AN: 301292 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 171664

African (AFR) AF: 0.00 AC: 0 AN: 8514

American (AMR) AF: 0.0000367 AC: 1 AN: 27232

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10778

East Asian (EAS) AF: 0.00 AC: 0 AN: 9206

South Asian (SAS) AF: 0.00 AC: 0 AN: 59618

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12356

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1148

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 158420

Other (OTH) AF: 0.00 AC: 0 AN: 14020

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 1193

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	9.5
DANN	Benign	0.73
PhyloP100		0.91

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: rs4728195; hg19: chr7-130034437;