rs1554421037

Variant names:

• chr7-130416950-T-C
• rs1554421037
• NM_018718.3:c.114A>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_018718.3(CEP41):​c.114A>G​(p.Lys38Lys) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CEP41 NM_018718.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.411
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 7-130416950-T-C is Benign according to our data. Variant chr7-130416950-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 540093.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.411 with no splicing effect.

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.114A>G	p.Lys38Lys	synonymous	Exon 3 of 11	NP_061188.1	Q9BYV8-1
	CEP41	NM_001257158.2		c.114A>G	p.Lys38Lys	synonymous	Exon 3 of 10	NP_001244087.1	Q9BYV8-2
	CEP41	NM_001257159.2		c.98-4710A>G		intron	N/A	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.114A>G	p.Lys38Lys	synonymous	Exon 3 of 11	ENSP00000223208.4	Q9BYV8-1
	CEP41	ENST00000343969.10	TSL:1	c.114A>G	p.Lys38Lys	synonymous	Exon 3 of 10	ENSP00000342738.6	A0A7I2PK71
	CEP41	ENST00000484549.6	TSL:1	n.*286A>G		non_coding_transcript_exon	Exon 3 of 11	ENSP00000419078.2	C9IZ34

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1434714 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 715626

African (AFR) AF: 0.00 AC: 0 AN: 32896

American (AMR) AF: 0.00 AC: 0 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25944

East Asian (EAS) AF: 0.00 AC: 0 AN: 39570

South Asian (SAS) AF: 0.00 AC: 0 AN: 85704

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53296

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5720

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1087366

Other (OTH) AF: 0.00 AC: 0 AN: 59522

GnomAD4 genome Cov.: 32

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	-0.53
CADD	Benign	7.8
DANN	Benign	0.58
PhyloP100		0.41
PromoterAI		0.0085	Neutral

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: rs1554421037; hg19: chr7-130056791;