8-95245668-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_177965.4(CFAP418):c.*1949C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0667 in 152,280 control chromosomes in the GnomAD database, including 416 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.067 (416 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CFAP418 NM_177965.4 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.358

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 8-95245668-G-C is Benign according to our data. Variant chr8-95245668-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 363987.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.086 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP418	NM_177965.4	c.*1949C>G		3_prime_UTR_variant	6/6	ENST00000286688.6
CFAP418	NM_001363260.1	c.*1949C>G		3_prime_UTR_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP418	ENST00000286688.6	c.*1949C>G		3_prime_UTR_variant	6/6	1	NM_177965.4	P1
CFAP418-AS1	ENST00000517655.1	n.521+40356G>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0667 AC: 10144 AN: 152162 Hom.: 415 Cov.: 32

Gnomad AFR AF: 0.0494

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0646

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0283

Gnomad FIN AF: 0.0306

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0879

Gnomad OTH AF: 0.0761

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 26 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 18

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0667 AC: 10155 AN: 152280 Hom.: 416 Cov.: 32 AF XY: 0.0628 AC XY: 4678 AN XY: 74474

Gnomad4 AFR AF: 0.0496

Gnomad4 AMR AF: 0.0646

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0284

Gnomad4 FIN AF: 0.0306

Gnomad4 NFE AF: 0.0879

Gnomad4 OTH AF: 0.0753

Alfa AF: 0.0339 Hom.: 24

Bravo AF: 0.0689

Asia WGS AF: 0.0150 AC: 54 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Cone-rod dystrophy 16 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Retinitis pigmentosa Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	1.2
Dann	Benign	0.70

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: rs117011452; hg19: chr8-96257896;