Variant 7-90282987-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001039706.3(CFAP69):c.1468G>A(p.Val490Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.791 in 1,593,122 control chromosomes in the GnomAD database, including 500,608 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.82 ( 51207 hom., cov: 32)

Exomes 𝑓: 0.79 ( 449401 hom. )

Consequence

CFAP69
NM_001039706.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.58

Variant links:

Genes affected

CFAP69 (HGNC:26107): (cilia and flagella associated protein 69) Acts upstream of or within sperm axoneme assembly. Located in cytoplasm and sperm midpiece. Implicated in spermatogenic failure 24. [provided by Alliance of Genome Resources, Apr 2022]

CFAP69 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.298084E-7).

BP6

Variant 7-90282987-G-A is Benign according to our data. Variant chr7-90282987-G-A is described in ClinVar as [Benign]. Clinvar id is 1192635.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP69	NM_001039706.3 linkuse as main transcript	c.1468G>A	p.Val490Met	missense_variant	13/23	ENST00000389297.8	NP_001034795.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP69	ENST00000389297.8 linkuse as main transcript	c.1468G>A	p.Val490Met	missense_variant	13/23	1	NM_001039706.3	ENSP00000373948	P1	A5D8W1-1

Frequencies

GnomAD3 genomes

AF:

0.818

AC:

124433

AN:

152084

Hom.:

51169

Cov.:

show subpopulations

Gnomad AFR

AF:

0.854

Gnomad AMI

AF:

0.803

Gnomad AMR

AF:

0.827

Gnomad ASJ

AF:

0.792

Gnomad EAS

AF:

0.997

Gnomad SAS

AF:

0.870

Gnomad FIN

AF:

0.869

Gnomad MID

AF:

0.835

Gnomad NFE

AF:

0.771

Gnomad OTH

AF:

0.808

GnomAD3 exomes

AF:

0.825

AC:

194826

AN:

236084

Hom.:

80806

AF XY:

0.821

AC XY:

105738

AN XY:

128718

show subpopulations

Gnomad AFR exome

AF:

0.855

Gnomad AMR exome

AF:

0.866

Gnomad ASJ exome

AF:

0.780

Gnomad EAS exome

AF:

0.998

Gnomad SAS exome

AF:

0.858

Gnomad FIN exome

AF:

0.864

Gnomad NFE exome

AF:

0.773

Gnomad OTH exome

AF:

0.802

GnomAD4 exome

AF:

0.788

AC:

1135454

AN:

1440920

Hom.:

449401

Cov.:

AF XY:

0.790

AC XY:

565961

AN XY:

716760

show subpopulations

Gnomad4 AFR exome

AF:

0.856

Gnomad4 AMR exome

AF:

0.864

Gnomad4 ASJ exome

AF:

0.781

Gnomad4 EAS exome

AF:

0.999

Gnomad4 SAS exome

AF:

0.857

Gnomad4 FIN exome

AF:

0.863

Gnomad4 NFE exome

AF:

0.767

Gnomad4 OTH exome

AF:

0.799

GnomAD4 genome

AF:

0.818

AC:

124523

AN:

152202

Hom.:

51207

Cov.:

AF XY:

0.823

AC XY:

61260

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.853

Gnomad4 AMR

AF:

0.827

Gnomad4 ASJ

AF:

0.792

Gnomad4 EAS

AF:

0.997

Gnomad4 SAS

AF:

0.871

Gnomad4 FIN

AF:

0.869

Gnomad4 NFE

AF:

0.771

Gnomad4 OTH

AF:

0.810

Alfa

AF:

0.782

Hom.:

110995

Bravo

AF:

0.816

TwinsUK

AF:

0.765

AC:

2835

ALSPAC

AF:

0.756

AC:

2915

ESP6500AA

AF:

0.860

AC:

3256

ESP6500EA

AF:

0.766

AC:

6284

ExAC

AF:

0.829

AC:

100155

Asia WGS

AF:

0.931

AC:

3233

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

CFAP69-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 16, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Spermatogenic failure 24

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Benign

0.10

DEOGEN2

Benign

0.013

T;.;.;.

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.38

T;T;T;T

MetaRNN

Benign

5.3e-7

T;T;T;T

MetaSVM

Benign

-0.95

MutationTaster

Benign

1.0

P;P;P

PROVEAN

Benign

0.23

N;N;N;N

REVEL

Benign

0.088

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.010

B;B;.;.

Vest4

0.038

MPC

0.064

ClinPred

0.0036

GERP RS

4.2

Varity_R

0.042

gMVP

0.21

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over