Genetic Variant CFAP410:p.Arg11Arg (chr21-44339162-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_004928.3(CFAP410):c.33G>A(p.Arg11Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 1,470,992 control chromosomes in the GnomAD database, including 42,087 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6648 hom., cov: 31)

Exomes 𝑓: 0.22 ( 35439 hom. )

Consequence

CFAP410
NM_004928.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0680

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:

ENSG00000232969 (HGNC:):

ENSG00000232969 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BP6

Variant 21-44339162-C-T is Benign according to our data. Variant chr21-44339162-C-T is described in ClinVar as [Benign]. Clinvar id is 259586.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.068 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP410	NM_004928.3 link	c.33G>A	p.Arg11Arg	synonymous_variant	Exon 1 of 7	ENST00000339818.9	NP_004919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CFAP410	ENST00000339818.9 link	c.33G>A	p.Arg11Arg	synonymous_variant	Exon 1 of 7	1	NM_004928.3	ENSP00000344566.4	O43822-1
CFAP410	ENST00000397956.7 link	c.33G>A	p.Arg11Arg	synonymous_variant	Exon 1 of 7	1		ENSP00000381047.3	O43822-4
CFAP410	ENST00000325223.7 link	c.33G>A	p.Arg11Arg	synonymous_variant	Exon 1 of 7	1		ENSP00000317302.7	O43822-3
ENSG00000232969	ENST00000426029.1 link	n.-214C>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.278

AC:

42128

AN:

151348

Hom.:

6642

Cov.:

show subpopulations

Gnomad AFR

AF:

0.425

Gnomad AMI

AF:

0.173

Gnomad AMR

AF:

0.257

Gnomad ASJ

AF:

0.186

Gnomad EAS

AF:

0.148

Gnomad SAS

AF:

0.378

Gnomad FIN

AF:

0.184

Gnomad MID

AF:

0.293

Gnomad NFE

AF:

0.217

Gnomad OTH

AF:

0.278

GnomAD3 exomes

AF:

0.240

AC:

21903

AN:

91162

Hom.:

2991

AF XY:

0.247

AC XY:

12666

AN XY:

51190

show subpopulations

Gnomad AFR exome

AF:

0.409

Gnomad AMR exome

AF:

0.250

Gnomad ASJ exome

AF:

0.182

Gnomad EAS exome

AF:

0.130

Gnomad SAS exome

AF:

0.354

Gnomad FIN exome

AF:

0.192

Gnomad NFE exome

AF:

0.210

Gnomad OTH exome

AF:

0.232

GnomAD4 exome

AF:

0.225

AC:

296327

AN:

1319536

Hom.:

35439

Cov.:

AF XY:

0.228

AC XY:

148263

AN XY:

650630

show subpopulations

Gnomad4 AFR exome

AF:

0.432

Gnomad4 AMR exome

AF:

0.262

Gnomad4 ASJ exome

AF:

0.182

Gnomad4 EAS exome

AF:

0.158

Gnomad4 SAS exome

AF:

0.356

Gnomad4 FIN exome

AF:

0.197

Gnomad4 NFE exome

AF:

0.213

Gnomad4 OTH exome

AF:

0.233

GnomAD4 genome

AF:

0.278

AC:

42175

AN:

151456

Hom.:

6648

Cov.:

AF XY:

0.277

AC XY:

20494

AN XY:

74026

show subpopulations

Gnomad4 AFR

AF:

0.425

Gnomad4 AMR

AF:

0.257

Gnomad4 ASJ

AF:

0.186

Gnomad4 EAS

AF:

0.149

Gnomad4 SAS

AF:

0.377

Gnomad4 FIN

AF:

0.184

Gnomad4 NFE

AF:

0.217

Gnomad4 OTH

AF:

0.278

Alfa

AF:

0.135

Hom.:

224

Bravo

AF:

0.288

Asia WGS

AF:

0.295

AC:

1012

AN:

3438

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 04, 2021

GeneDx

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

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.96

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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