8-95245454-A-G

Position:

• chr8-95245454-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_177965.4(CFAP418):​c.*2163T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0465 in 152,296 control chromosomes in the GnomAD database, including 244 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.047 (244 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CFAP418 NM_177965.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.374

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 8-95245454-A-G is Benign according to our data. Variant chr8-95245454-A-G is described in ClinVar as [Benign]. Clinvar id is 363984.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP418	NM_177965.4	c.*2163T>C		3_prime_UTR_variant	6/6	ENST00000286688.6	NP_808880.1
CFAP418	NM_001363260.1	c.*2163T>C		3_prime_UTR_variant	5/5		NP_001350189.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP418	ENST00000286688.6	c.*2163T>C		3_prime_UTR_variant	6/6	1	NM_177965.4	ENSP00000286688	P1
CFAP418-AS1	ENST00000517655.1	n.521+40142A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0465 AC: 7076 AN: 152178 Hom.: 242 Cov.: 32

Gnomad AFR AF: 0.0103

Gnomad AMI AF: 0.0747

Gnomad AMR AF: 0.0248

Gnomad ASJ AF: 0.0398

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0577

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0603

Gnomad OTH AF: 0.0387

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0465 AC: 7085 AN: 152296 Hom.: 244 Cov.: 32 AF XY: 0.0469 AC XY: 3496 AN XY: 74468

Gnomad4 AFR AF: 0.0102

Gnomad4 AMR AF: 0.0248

Gnomad4 ASJ AF: 0.0398

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.0577

Gnomad4 NFE AF: 0.0603

Gnomad4 OTH AF: 0.0430

Alfa AF: 0.0515 Hom.: 31

Bravo AF: 0.0412

Asia WGS AF: 0.117 AC: 408 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Cone-rod dystrophy 16 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.66

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: rs75940981; hg19: chr8-96257682;