rs766087213

chr8-95260472-T-A

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_177965.4(CFAP418):c.304A>T(p.Lys102Ter) 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
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.72

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

ACMG classification

Verdict is Pathogenic. Variant got 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 id is 417789.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr8-95260472-T-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP418	NM_177965.4	c.304A>T	p.Lys102Ter	stop_gained	3/6	ENST00000286688.6
CFAP418	NM_001363260.1	c.304A>T	p.Lys102Ter	stop_gained	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP418	ENST00000286688.6	c.304A>T	p.Lys102Ter	stop_gained	3/6	1	NM_177965.4	P1
CFAP418-AS1	ENST00000517655.1	n.521+55160T>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000884 AC: 2 AN: 226344 Hom.: 0 AF XY: 0.00000814 AC XY: 1 AN XY: 122810

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 SAS 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: 4 AN: 1435082 Hom.: 0 Cov.: 28 AF XY: 0.00000420 AC XY: 3 AN XY: 713922

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000363

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000312 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Bardet-biedl syndrome 21 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 28, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.61	D
BayesDel_noAF	Pathogenic	0.62
Cadd	Pathogenic	37
Dann	Uncertain	1.0
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.94	D
MutationTaster	Benign	1.0	A
Vest4		0.49
GERP RS		5.7

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

LitVar

Other links and lift over

dbSNP: rs766087213; hg19: chr8-96272700;