rs79305170

Variant names:

• chr8-95245405-G-A
• rs79305170
• NM_177965.4:c.*2212C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-95245405-G-A
• chr8-95245405-G-C

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.*2212C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0166 in 152,212 control chromosomes in the GnomAD database, including 42 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 0.017 (42 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: -1.67
• 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=-0.89).
• BP6: Variant 8-95245405-G-A is Benign according to our data. Variant chr8-95245405-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 912347.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0166 (2533/152212) while in subpopulation NFE AF = 0.0189 (1285/68018). AF 95% confidence interval is 0.018. There are 42 homozygotes in GnomAd4. There are 1411 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 42 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.*2212C>T		3_prime_UTR	Exon 6 of 6	NP_808880.1	Q96NL8
	CFAP418	NM_001363260.1		c.*2212C>T		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.*2212C>T		3_prime_UTR	Exon 6 of 6	ENSP00000286688.5	Q96NL8
	CFAP418	ENST00000945329.1		c.*2212C>T		3_prime_UTR	Exon 5 of 5	ENSP00000615388.1
	CFAP418-AS1	ENST00000517655.1	TSL:4	n.521+40093G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0166 AC: 2521 AN: 152094 Hom.: 38 Cov.: 32

Gnomad AFR AF: 0.00326

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0142

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.00500

Gnomad SAS AF: 0.0172

Gnomad FIN AF: 0.0630

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0189

Gnomad OTH AF: 0.0144

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

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) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.0166 AC: 2533 AN: 152212 Hom.: 42 Cov.: 32 AF XY: 0.0190 AC XY: 1411 AN XY: 74416

African (AFR) AF: 0.00330 AC: 137 AN: 41528

American (AMR) AF: 0.0142 AC: 217 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0167 AC: 58 AN: 3470

East Asian (EAS) AF: 0.00501 AC: 26 AN: 5192

South Asian (SAS) AF: 0.0172 AC: 83 AN: 4830

European-Finnish (FIN) AF: 0.0630 AC: 666 AN: 10574

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0189 AC: 1285 AN: 68018

Other (OTH) AF: 0.0194 AC: 41 AN: 2110

Alfa AF: 0.00973 Hom.: 1

Bravo AF: 0.0117

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	-0.89
CADD	Benign	0.17
DANN	Benign	0.22
PhyloP100		-1.7
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: rs79305170; hg19: chr8-96257633;