Genetic Variant CFAP418:p.Lys102* (chr8-95260472-T-A) – ACMG Classification: Pathogenic (11 pts)

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_177965.4(CFAP418):c.304A>T(p.Lys102*) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000279 in 1,435,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

CFAP418
NM_177965.4 stop_gained

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 4.72

Publications

0 publications found

Variant links:

Genes affected

CFAP418 (HGNC:27232): (cilia and flagella associated protein 418) This gene encodes a ubiquitously expressed protein of unknown function. It has high levels of mRNA expression in the brain, heart, and retina and the protein co-localizes with polyglutamylated tubulin at the base of the primary cilium in human retinal pigment epithelial cells. Mutations in this gene have been associated with autosomal recessive cone-rod dystrophy (arCRD) and retinitis pigmentosa (arRP). [provided by RefSeq, Mar 2012]

CFAP418 links:

CFAP418-AS1 (HGNC:50444): (CFAP418 antisense RNA 1)

CFAP418-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Pathogenic. The variant received 11 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 8-95260472-T-A is Pathogenic according to our data. Variant chr8-95260472-T-A is described in ClinVar as Pathogenic. ClinVar VariationId is 417789.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177965.4. 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
	CFAP418	NM_177965.4	MANE Select	c.304A>T	p.Lys102*	stop_gained	Exon 3 of 6	NP_808880.1
	CFAP418	NM_001363260.1		c.304A>T	p.Lys102*	stop_gained	Exon 3 of 5	NP_001350189.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP418	ENST00000286688.6	TSL:1 MANE Select	c.304A>T	p.Lys102*	stop_gained	Exon 3 of 6	ENSP00000286688.5
	CFAP418-AS1	ENST00000517655.1	TSL:4	n.521+55160T>A		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000884

AC:

AN:

226344

AF XY:

0.00000814

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000187

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000279

AC:

AN:

1435082

Hom.:

Cov.:

AF XY:

0.00000420

AC XY:

AN XY:

713922

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31512

American (AMR)

AF:

0.00

AC:

AN:

37650

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25520

East Asian (EAS)

AF:

0.00

AC:

AN:

38454

South Asian (SAS)

AF:

0.00

AC:

AN:

80800

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53208

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.00000363

AC:

AN:

1102828

Other (OTH)

AF:

0.00

AC:

AN:

59408

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Bardet-biedl syndrome 21

Pathogenic:1

Mar 28, 2017

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.61

BayesDel_noAF

Pathogenic

0.62

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Pathogenic

0.84

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Uncertain

0.94

PhyloP100

4.7

Vest4

0.49

GERP RS

5.7

Mutation Taster

=21/179

disease causing (ClinVar)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over