7-130394596-C-G

Variant names:

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

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.*4295G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 453,184 control chromosomes in the GnomAD database, including 27,615 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (10260 hom., cov: 31)
  • Exomes 𝑓: 0.33 (17355 hom.)
• Consequence: CEP41 NM_018718.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 7-130394596-C-G is Benign according to our data. Variant chr7-130394596-C-G is described in ClinVar as Benign. ClinVar VariationId is 358896.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

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>C		3_prime_UTR	Exon 11 of 11	NP_061188.1	Q9BYV8-1
	CEP41	NM_001257158.2		c.*4295G>C		3_prime_UTR	Exon 10 of 10	NP_001244087.1	Q9BYV8-2
	CEP41	NM_001257159.2		c.*4295G>C		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>C		3_prime_UTR	Exon 11 of 11	ENSP00000223208.4	Q9BYV8-1
	CEP41	ENST00000541543.6	TSL:2	c.*4295G>C		3_prime_UTR	Exon 11 of 11	ENSP00000445888.2	A0A7I2SYM4
	CEP41	ENST00000675649.1		c.*4295G>C		3_prime_UTR	Exon 9 of 9	ENSP00000502385.1	A0A6Q8PGR4

Frequencies

GnomAD3 genomes AF: 0.361 AC: 54866 AN: 151798 Hom.: 10256 Cov.: 31

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.365

GnomAD2 exomes AF: 0.323 AC: 41236 AN: 127810 AF XY: 0.324

Gnomad AFR exome AF: 0.452

Gnomad AMR exome AF: 0.263

Gnomad ASJ exome AF: 0.389

Gnomad EAS exome AF: 0.247

Gnomad FIN exome AF: 0.328

Gnomad NFE exome AF: 0.341

Gnomad OTH exome AF: 0.349

GnomAD4 exome AF: 0.334 AC: 100701 AN: 301268 Hom.: 17355 Cov.: 0 AF XY: 0.333 AC XY: 57242 AN XY: 171646

African (AFR) AF: 0.437 AC: 3718 AN: 8512

American (AMR) AF: 0.263 AC: 7164 AN: 27226

Ashkenazi Jewish (ASJ) AF: 0.388 AC: 4180 AN: 10776

East Asian (EAS) AF: 0.238 AC: 2195 AN: 9206

South Asian (SAS) AF: 0.322 AC: 19211 AN: 59612

European-Finnish (FIN) AF: 0.340 AC: 4196 AN: 12356

Middle Eastern (MID) AF: 0.451 AC: 518 AN: 1148

European-Non Finnish (NFE) AF: 0.345 AC: 54703 AN: 158412

Other (OTH) AF: 0.344 AC: 4816 AN: 14020

GnomAD4 genome AF: 0.361 AC: 54897 AN: 151916 Hom.: 10260 Cov.: 31 AF XY: 0.356 AC XY: 26428 AN XY: 74236

African (AFR) AF: 0.445 AC: 18435 AN: 41410

American (AMR) AF: 0.310 AC: 4739 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1352 AN: 3470

East Asian (EAS) AF: 0.231 AC: 1190 AN: 5160

South Asian (SAS) AF: 0.313 AC: 1503 AN: 4804

European-Finnish (FIN) AF: 0.321 AC: 3385 AN: 10540

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.341 AC: 23157 AN: 67936

Other (OTH) AF: 0.365 AC: 771 AN: 2112

Alfa AF: 0.287 Hom.: 1193

Bravo AF: 0.362

Asia WGS AF: 0.229 AC: 797 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Joubert syndrome 15 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	10
DANN	Benign	0.60
PhyloP100		0.91
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: rs4728195; hg19: chr7-130034437;