rs4453686

Variant names:

• chr2-219031828-C-G
• rs4453686
• NM_194302.4:c.646-170G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

CFAP65 Gene-Disease associations (from GenCC):

• non-syndromic male infertility due to sperm motility disorder

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• spermatogenic failure 40

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194302.4. 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
	CFAP65	NM_194302.4	MANE Select	c.646-170G>C		intron	N/A	NP_919278.2	Q6ZU64-1
	CFAP65	NM_001278295.1		c.613-170G>C		intron	N/A	NP_001265224.1	Q49A14
	CFAP65	NM_001278296.2		c.451-170G>C		intron	N/A	NP_001265225.1	Q6ZU64-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP65	ENST00000341552.10	TSL:5 MANE Select	c.646-170G>C		intron	N/A	ENSP00000340776.5	Q6ZU64-1
	CFAP65	ENST00000453220.5	TSL:5	c.646-170G>C		intron	N/A	ENSP00000409117.1	Q6ZU64-1
	CFAP65	ENST00000409865.7	TSL:2	c.613-170G>C		intron	N/A	ENSP00000386945.3	Q6ZU64-5

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

African (AFR) AF: 0.592 AC: 24532 AN: 41464

American (AMR) AF: 0.168 AC: 2568 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 484 AN: 3466

East Asian (EAS) AF: 0.145 AC: 748 AN: 5170

South Asian (SAS) AF: 0.158 AC: 758 AN: 4812

European-Finnish (FIN) AF: 0.114 AC: 1199 AN: 10542

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8524 AN: 67960

Other (OTH) AF: 0.247 AC: 522 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.5
DANN	Benign	0.67
PhyloP100		-0.10
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: rs4453686; hg19: chr2-219896550;