rs75087725

Variant names:

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBS1BS2

The NM_004928.3(CFAP410):c.172G>T(p.Val58Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00998 in 1,612,464 control chromosomes in the GnomAD database, including 105 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 (★★).

Frequency

Genomes: 𝑓 0.0088 ( 16 hom., cov: 34)

Exomes 𝑓: 0.010 ( 89 hom. )

Consequence

CFAP410
NM_004928.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.292

Variant links:

Genes affected

CFAP410 (HGNC:1260): (cilia and flagella associated protein 410) Four alternatively spliced transcript variants encoding four different isoforms have been found for this nuclear gene. All isoforms contain leucine-rich repeats. Three of these isoforms are mitochondrial proteins and one of them lacks the target peptide, so is not located in mitochondrion. This gene is down-regulated in Down syndrome (DS) brain, which may represent mitochondrial dysfunction in DS patients. [provided by RefSeq, Sep 2012]

CFAP410 links:

ENSG00000184441 (HGNC:):

ENSG00000184441 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

PM1

In a chain Cilia- and flagella-associated protein 410 (size 255) in uniprot entity CF410_HUMAN there are 22 pathogenic changes around while only 9 benign (71%) in NM_004928.3

BP4

Computational evidence support a benign effect (MetaRNN=0.0025855005).

BP6

Variant 21-44333234-C-A is Benign according to our data. Variant chr21-44333234-C-A is described in ClinVar as [Benign]. Clinvar id is 259585.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr21-44333234-C-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00882 (1344/152380) while in subpopulation AMR AF= 0.0119 (182/15314). AF 95% confidence interval is 0.0112. There are 16 homozygotes in gnomad4. There are 712 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP410	NM_004928.3 link	c.172G>T	p.Val58Leu	missense_variant	Exon 4 of 7	ENST00000339818.9	NP_004919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP410	ENST00000339818.9 link	c.172G>T	p.Val58Leu	missense_variant	Exon 4 of 7	1	NM_004928.3	ENSP00000344566.4		O43822-1

Frequencies

GnomAD3 genomes

AF:

0.00882

AC:

1343

AN:

152262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00171

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0119

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.0236

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0119

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00798

AC:

1933

AN:

242326

Hom.:

AF XY:

0.00811

AC XY:

1069

AN XY:

131888

show subpopulations

Gnomad AFR exome

AF:

0.00128

Gnomad AMR exome

AF:

0.00516

Gnomad ASJ exome

AF:

0.000407

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00118

Gnomad FIN exome

AF:

0.0227

Gnomad NFE exome

AF:

0.0109

Gnomad OTH exome

AF:

0.00774

GnomAD4 exome

AF:

0.0101

AC:

14747

AN:

1460084

Hom.:

Cov.:

AF XY:

0.00983

AC XY:

7141

AN XY:

726240

show subpopulations

Gnomad4 AFR exome

AF:

0.00146

Gnomad4 AMR exome

AF:

0.00484

Gnomad4 ASJ exome

AF:

0.000306

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000964

Gnomad4 FIN exome

AF:

0.0216

Gnomad4 NFE exome

AF:

0.0115

Gnomad4 OTH exome

AF:

0.00795

GnomAD4 genome

AF:

0.00882

AC:

1344

AN:

152380

Hom.:

Cov.:

AF XY:

0.00956

AC XY:

712

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.00171

Gnomad4 AMR

AF:

0.0119

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.0236

Gnomad4 NFE

AF:

0.0119

Gnomad4 OTH

AF:

0.00804

Alfa

AF:

0.0101

Hom.:

Bravo

AF:

0.00673

TwinsUK

AF:

0.0127

AC:

ALSPAC

AF:

0.0140

AC:

ESP6500AA

AF:

0.000682

AC:

ESP6500EA

AF:

0.0106

AC:

ExAC

AF:

0.00731

AC:

887

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0109

EpiControl

AF:

0.0106

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

CFAP410: BP4, BS1, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.84

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.0064

T;.;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.076

LIST_S2

Benign

0.82

T;T;T

MetaRNN

Benign

0.0026

T;T;T

MetaSVM

Benign

-0.92

PROVEAN

Benign

-0.22

N;N;N

REVEL

Benign

0.023

Sift

Benign

0.48

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.015

B;.;.

Vest4

0.26

MutPred

0.46

Gain of disorder (P = 0.1069);Gain of disorder (P = 0.1069);Gain of disorder (P = 0.1069);

MVP

0.061

MPC

0.25

ClinPred

0.0084

GERP RS

-0.56

Varity_R

0.041

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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