Genetic Variant CFAP410:p.Arg11Arg (chr21-44339162-C-G) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_004928.3(CFAP410):c.33G>C(p.Arg11Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000151 in 1,321,348 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. R11R) has been classified as Benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

CFAP410
NM_004928.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0680

Publications

19 publications found

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 Gene-Disease associations (from GenCC):

axial spondylometaphyseal dysplasia
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
amyotrophic lateral sclerosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
cone-rod dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CFAP410 links:

ENSG00000232969 (HGNC:):

ENSG00000232969 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 21-44339162-C-G is Benign according to our data. Variant chr21-44339162-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1937569.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.068 with no splicing effect.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000151

AC:

AN:

1321348

Hom.:

Cov.:

AF XY:

0.00000153

AC XY:

AN XY:

651634

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26622

American (AMR)

AF:

0.00

AC:

AN:

25064

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23136

East Asian (EAS)

AF:

0.0000714

AC:

AN:

28020

South Asian (SAS)

AF:

0.00

AC:

AN:

71204

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46762

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5328

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1041080

Other (OTH)

AF:

0.00

AC:

AN:

54132

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

224

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 25, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely 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

-0.39

CADD

Benign

(source)

DANN

Benign

0.85

PhyloP100

0.068

PromoterAI

-0.022

Neutral

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over