rs4453686

Positions:

• chr2-219031828-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_194302.4(CFAP65):​c.646-170G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 152,014 control chromosomes in the GnomAD database, including 8,330 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.26 (8330 hom., cov: 33)
• Consequence: CFAP65 NM_194302.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.105

Genes affected

CFAP65 (HGNC:25325): (cilia and flagella associated protein 65) The protein encoded by this gene has putative coiled-coil domains and may be a transmembrane protein. The chicken ortholog of this gene is involved in the Rose-comb mutation, which is a large chromosome inversion, resulting in altered comb morphology and defects in sperm motility. [provided by RefSeq, Aug 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP65	NM_194302.4	c.646-170G>C		intron_variant		ENST00000341552.10	NP_919278.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP65	ENST00000341552.10	c.646-170G>C		intron_variant		5	NM_194302.4	ENSP00000340776.5

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39433 AN: 151896 Hom.: 8304 Cov.: 33

Gnomad AFR AF: 0.592

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.248

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.260 AC: 39502 AN: 152014 Hom.: 8330 Cov.: 33 AF XY: 0.254 AC XY: 18914 AN XY: 74330

Gnomad4 AFR AF: 0.592

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.247

Alfa AF: 0.199 Hom.: 656

Bravo AF: 0.277

Asia WGS AF: 0.204 AC: 708 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.5
DANN	Benign	0.67

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: rs4453686; hg19: chr2-219896550;