8-95245092-A-G

Variant names:

• chr8-95245092-A-G
• rs74318654
• NM_177965.4:c.*2525T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_177965.4(CFAP418):​c.*2525T>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 0.048 in 152,252 control chromosomes in the GnomAD database, including 255 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.048 (255 hom., cov: 32)
  • 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: 0.194
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 8-95245092-A-G is Benign according to our data. Variant chr8-95245092-A-G is described in ClinVar as Benign. ClinVar VariationId is 363981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

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.*2525T>C		3_prime_UTR	Exon 6 of 6	NP_808880.1	Q96NL8
	CFAP418	NM_001363260.1		c.*2525T>C		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.*2525T>C		3_prime_UTR	Exon 6 of 6	ENSP00000286688.5	Q96NL8
	CFAP418	ENST00000945329.1		c.*2525T>C		3_prime_UTR	Exon 5 of 5	ENSP00000615388.1
	CFAP418-AS1	ENST00000517655.1	TSL:4	n.521+39780A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0480 AC: 7301 AN: 152134 Hom.: 253 Cov.: 32

Gnomad AFR AF: 0.0106

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.0348

Gnomad ASJ AF: 0.0398

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0573

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0603

Gnomad OTH AF: 0.0406

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 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) AC: 0 AN: 0

GnomAD4 genome AF: 0.0480 AC: 7311 AN: 152252 Hom.: 255 Cov.: 32 AF XY: 0.0487 AC XY: 3628 AN XY: 74448

African (AFR) AF: 0.0106 AC: 440 AN: 41566

American (AMR) AF: 0.0347 AC: 531 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0398 AC: 138 AN: 3468

East Asian (EAS) AF: 0.146 AC: 756 AN: 5188

South Asian (SAS) AF: 0.117 AC: 566 AN: 4826

European-Finnish (FIN) AF: 0.0573 AC: 606 AN: 10576

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0603 AC: 4098 AN: 68014

Other (OTH) AF: 0.0449 AC: 95 AN: 2114

Alfa AF: 0.0548 Hom.: 44

Bravo AF: 0.0439

Asia WGS AF: 0.118 AC: 407 AN: 3448

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Cone-rod dystrophy 16 (1)
-	-	1	not provided (1)
-	-	1	Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.5
DANN	Benign	0.88
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism (auto)

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: rs74318654; hg19: chr8-96257320;