chr8-95245451-A-C

Variant names:

• chr8-95245451-A-C
• rs149998549
• NM_177965.4:c.*2166T>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_177965.4(CFAP418):​c.*2166T>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 0.0147 in 152,304 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.015 (27 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CFAP418 NM_177965.4 3_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 1.45
• 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 8-95245451-A-C is Benign according to our data. Variant chr8-95245451-A-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 912349.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0147 (2246/152304) while in subpopulation NFE AF = 0.0236 (1602/68020). AF 95% confidence interval is 0.0226. There are 27 homozygotes in GnomAd4. There are 1060 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 27 AR gene

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.*2166T>G		3_prime_UTR	Exon 6 of 6	NP_808880.1	Q96NL8
	CFAP418	NM_001363260.1		c.*2166T>G		3_prime_UTR	Exon 5 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.*2166T>G		3_prime_UTR	Exon 6 of 6	ENSP00000286688.5	Q96NL8
	CFAP418	ENST00000945329.1		c.*2166T>G		3_prime_UTR	Exon 5 of 5	ENSP00000615388.1
	CFAP418-AS1	ENST00000517655.1	TSL:4	n.521+40139A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0148 AC: 2246 AN: 152186 Hom.: 27 Cov.: 32

Gnomad AFR AF: 0.00391

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0113

Gnomad ASJ AF: 0.0156

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.00848

Gnomad FIN AF: 0.0156

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0235

Gnomad OTH AF: 0.0153

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0147 AC: 2246 AN: 152304 Hom.: 27 Cov.: 32 AF XY: 0.0142 AC XY: 1060 AN XY: 74466

African (AFR) AF: 0.00390 AC: 162 AN: 41570

American (AMR) AF: 0.0113 AC: 172 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0156 AC: 54 AN: 3472

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5184

South Asian (SAS) AF: 0.00849 AC: 41 AN: 4830

European-Finnish (FIN) AF: 0.0156 AC: 166 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0236 AC: 1602 AN: 68020

Other (OTH) AF: 0.0151 AC: 32 AN: 2114

Alfa AF: 0.0176 Hom.: 8

Bravo AF: 0.0135

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	-	1	Cone-rod dystrophy 16 (1)
-	1	-	Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.7
DANN	Benign	0.52
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs149998549; hg19: chr8-96257679;