chr7-130393789-C-T

Variant names:

• chr7-130393789-C-T
• rs1990790
• NM_018718.3:c.*5102G>A

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.*5102G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.519 in 451,426 control chromosomes in the GnomAD database, including 61,491 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.54 (22332 hom., cov: 32)
  • Exomes 𝑓: 0.51 (39159 hom.)
• Consequence: CEP41 NM_018718.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.53
• Publications: 21 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: Labcorp Genetics (formerly Invitae), G2P
• 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=-0.92).
• BP6: Variant 7-130393789-C-T is Benign according to our data. Variant chr7-130393789-C-T is described in ClinVar as Benign. ClinVar VariationId is 358883.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.625 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP41	NM_018718.3	MANE Select	c.*5102G>A		3_prime_UTR	Exon 11 of 11	NP_061188.1
	CEP41	NM_001257158.2		c.*5102G>A		3_prime_UTR	Exon 10 of 10	NP_001244087.1
	CEP41	NM_001257159.2		c.*5102G>A		3_prime_UTR	Exon 9 of 9	NP_001244088.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP41	ENST00000223208.10	TSL:1 MANE Select	c.*5102G>A		3_prime_UTR	Exon 11 of 11	ENSP00000223208.4
	CEP41	ENST00000541543.6	TSL:2	c.*5102G>A		3_prime_UTR	Exon 11 of 11	ENSP00000445888.2
	CEP41	ENST00000675649.1		c.*5102G>A		3_prime_UTR	Exon 9 of 9	ENSP00000502385.1

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81707 AN: 151922 Hom.: 22294 Cov.: 32

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.523

GnomAD2 exomes AF: 0.509 AC: 64518 AN: 126670 AF XY: 0.511

Gnomad AFR exome AF: 0.636

Gnomad AMR exome AF: 0.470

Gnomad ASJ exome AF: 0.545

Gnomad EAS exome AF: 0.492

Gnomad FIN exome AF: 0.499

Gnomad NFE exome AF: 0.506

Gnomad OTH exome AF: 0.521

GnomAD4 exome AF: 0.510 AC: 152600 AN: 299386 Hom.: 39159 Cov.: 0 AF XY: 0.511 AC XY: 87160 AN XY: 170602

African (AFR) AF: 0.634 AC: 5291 AN: 8340

American (AMR) AF: 0.472 AC: 12694 AN: 26906

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 5791 AN: 10680

East Asian (EAS) AF: 0.499 AC: 4582 AN: 9188

South Asian (SAS) AF: 0.521 AC: 30926 AN: 59334

European-Finnish (FIN) AF: 0.498 AC: 6133 AN: 12320

Middle Eastern (MID) AF: 0.554 AC: 633 AN: 1142

European-Non Finnish (NFE) AF: 0.503 AC: 79305 AN: 157570

Other (OTH) AF: 0.521 AC: 7245 AN: 13906

GnomAD4 genome AF: 0.538 AC: 81805 AN: 152040 Hom.: 22332 Cov.: 32 AF XY: 0.535 AC XY: 39748 AN XY: 74280

African (AFR) AF: 0.632 AC: 26190 AN: 41470

American (AMR) AF: 0.496 AC: 7580 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1912 AN: 3470

East Asian (EAS) AF: 0.496 AC: 2568 AN: 5174

South Asian (SAS) AF: 0.512 AC: 2468 AN: 4822

European-Finnish (FIN) AF: 0.493 AC: 5188 AN: 10528

Middle Eastern (MID) AF: 0.497 AC: 145 AN: 292

European-Non Finnish (NFE) AF: 0.501 AC: 34052 AN: 67988

Other (OTH) AF: 0.526 AC: 1110 AN: 2110

Alfa AF: 0.512 Hom.: 30086

Bravo AF: 0.542

Asia WGS AF: 0.510 AC: 1771 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	-0.92
CADD	Benign	0.0060
DANN	Benign	0.45
PhyloP100		-1.5
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: rs1990790; hg19: chr7-130033630;