rs760160179

Variant names:

• chr7-130393918-G-A
• rs760160179
• NM_018718.3:c.*4973C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-130393918-G-A
• chr7-130393918-G-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BS1_Supporting

The NM_018718.3(CEP41):​c.*4973C>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 0.000405 in 453,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00032 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00045 (0 hom.)
• Consequence: CEP41 NM_018718.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.279
• 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000322 (49/152062) while in subpopulation NFE AF = 0.000559 (38/68006). AF 95% confidence interval is 0.000418. There are 0 homozygotes in GnomAd4. There are 27 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

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.*4973C>T		3_prime_UTR	Exon 11 of 11	NP_061188.1	Q9BYV8-1
	CEP41	NM_001257158.2		c.*4973C>T		3_prime_UTR	Exon 10 of 10	NP_001244087.1	Q9BYV8-2
	CEP41	NM_001257159.2		c.*4973C>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.*4973C>T		3_prime_UTR	Exon 11 of 11	ENSP00000223208.4	Q9BYV8-1
	CEP41	ENST00000541543.6	TSL:2	c.*4973C>T		3_prime_UTR	Exon 11 of 11	ENSP00000445888.2	A0A7I2SYM4
	CEP41	ENST00000675649.1		c.*4973C>T		3_prime_UTR	Exon 9 of 9	ENSP00000502385.1	A0A6Q8PGR4

Frequencies

GnomAD3 genomes AF: 0.000322 AC: 49 AN: 152062 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000559

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000461 AC: 59 AN: 128028 AF XY: 0.000456

Gnomad AFR exome AF: 0.000164

Gnomad AMR exome AF: 0.000657

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000740

Gnomad OTH exome AF: 0.00175

GnomAD4 exome AF: 0.000447 AC: 135 AN: 301794 Hom.: 0 Cov.: 0 AF XY: 0.000407 AC XY: 70 AN XY: 171996

African (AFR) AF: 0.000117 AC: 1 AN: 8554

American (AMR) AF: 0.000770 AC: 21 AN: 27274

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 9210

South Asian (SAS) AF: 0.00 AC: 0 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: 0.000680 AC: 108 AN: 158764

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

GnomAD4 genome AF: 0.000322 AC: 49 AN: 152062 Hom.: 0 Cov.: 32 AF XY: 0.000364 AC XY: 27 AN XY: 74272

African (AFR) AF: 0.000121 AC: 5 AN: 41384

American (AMR) AF: 0.000262 AC: 4 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000559 AC: 38 AN: 68006

Other (OTH) AF: 0.000957 AC: 2 AN: 2090

Alfa AF: 0.000598 Hom.: 0

Bravo AF: 0.000438

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

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	-0.87
CADD	Benign	4.2
DANN	Benign	0.87
PhyloP100		0.28

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: rs760160179; hg19: chr7-130033759;