NM_018718.3:c.*4594C>T

Variant names:

• chr7-130394297-G-A
• rs151309255
• NM_018718.3:c.*4594C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_018718.3(CEP41):​c.*4594C>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 0.000784 in 453,996 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00042 (1 hom.)
• Consequence: CEP41 NM_018718.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.228
• Publications: 0 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 7-130394297-G-A is Benign according to our data. Variant chr7-130394297-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 912136.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0015 (228/152202) while in subpopulation EAS AF = 0.00579 (30/5182). AF 95% confidence interval is 0.00417. There are 1 homozygotes in GnomAd4. There are 105 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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.*4594C>T		3_prime_UTR	Exon 11 of 11	NP_061188.1	Q9BYV8-1
	CEP41	NM_001257158.2		c.*4594C>T		3_prime_UTR	Exon 10 of 10	NP_001244087.1	Q9BYV8-2
	CEP41	NM_001257159.2		c.*4594C>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.*4594C>T		3_prime_UTR	Exon 11 of 11	ENSP00000223208.4	Q9BYV8-1
	CEP41	ENST00000541543.6	TSL:2	c.*4594C>T		3_prime_UTR	Exon 11 of 11	ENSP00000445888.2	A0A7I2SYM4
	CEP41	ENST00000675649.1		c.*4594C>T		3_prime_UTR	Exon 9 of 9	ENSP00000502385.1	A0A6Q8PGR4

Frequencies

GnomAD3 genomes AF: 0.00150 AC: 228 AN: 152084 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00454

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000459

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00578

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000961

GnomAD2 exomes AF: 0.000883 AC: 113 AN: 128028 AF XY: 0.000628

Gnomad AFR exome AF: 0.00362

Gnomad AMR exome AF: 0.000123

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00824

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000211

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000424 AC: 128 AN: 301794 Hom.: 1 Cov.: 0 AF XY: 0.000308 AC XY: 53 AN XY: 171996

African (AFR) AF: 0.00456 AC: 39 AN: 8554

American (AMR) AF: 0.000110 AC: 3 AN: 27274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10786

East Asian (EAS) AF: 0.00825 AC: 76 AN: 9210

South Asian (SAS) AF: 0.0000503 AC: 3 AN: 59650

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1150

European-Non Finnish (NFE) AF: 0.0000126 AC: 2 AN: 158764

Other (OTH) AF: 0.000356 AC: 5 AN: 14042

GnomAD4 genome AF: 0.00150 AC: 228 AN: 152202 Hom.: 1 Cov.: 32 AF XY: 0.00141 AC XY: 105 AN XY: 74414

African (AFR) AF: 0.00453 AC: 188 AN: 41508

American (AMR) AF: 0.000458 AC: 7 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00579 AC: 30 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68012

Other (OTH) AF: 0.000951 AC: 2 AN: 2104

Alfa AF: 0.00108 Hom.: 0

Bravo AF: 0.00152

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Joubert syndrome 15 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.3
DANN	Benign	0.73
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism

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: rs151309255; hg19: chr7-130034138;