8-95260472-T-C

Variant names:

• chr8-95260472-T-C
• rs766087213
• NM_177965.4:c.304A>G
• CFAP418 p.Lys102Glu

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_177965.4(CFAP418):​c.304A>G​(p.Lys102Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000000697 in 1,435,082 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: CFAP418 NM_177965.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.72
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP418	NM_177965.4	MANE Select	c.304A>G	p.Lys102Glu	missense	Exon 3 of 6	NP_808880.1	Q96NL8
	CFAP418	NM_001363260.1		c.304A>G	p.Lys102Glu	missense	Exon 3 of 5	NP_001350189.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP418	ENST00000286688.6	TSL:1 MANE Select	c.304A>G	p.Lys102Glu	missense	Exon 3 of 6	ENSP00000286688.5	Q96NL8
	CFAP418	ENST00000945329.1		c.304A>G	p.Lys102Glu	missense	Exon 3 of 5	ENSP00000615388.1
	CFAP418-AS1	ENST00000517655.1	TSL:4	n.521+55160T>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.97e-7 AC: 1 AN: 1435082 Hom.: 0 Cov.: 28 AF XY: 0.00000140 AC XY: 1 AN XY: 713922

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31512

American (AMR) AF: 0.00 AC: 0 AN: 37650

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25520

East Asian (EAS) AF: 0.00 AC: 0 AN: 38454

South Asian (SAS) AF: 0.00 AC: 0 AN: 80800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53208

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5702

European-Non Finnish (NFE) AF: 9.07e-7 AC: 1 AN: 1102828

Other (OTH) AF: 0.00 AC: 0 AN: 59408

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	D
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.075	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Uncertain	0.49	D
MutationAssessor	Uncertain	2.7	M
PhyloP100		4.7
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.52
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.025	D
Varity_R		0.30
gMVP		0.38
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs766087213;

hg19: chr8-96272700;