rs11552066

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004928.3(CFAP410):c.707A>G(p.Gln236Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,602,162 control chromosomes in the GnomAD database, including 9,802 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q236W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.093 ( 742 hom., cov: 34)

Exomes 𝑓: 0.11 ( 9060 hom. )

Consequence

CFAP410
NM_004928.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.07

Publications

18 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:

ENSG00000241728 (HGNC:):

ENSG00000241728 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013685822).

BP6

Variant 21-44330262-T-C is Benign according to our data. Variant chr21-44330262-T-C is described in ClinVar as Benign. ClinVar VariationId is 259589.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004928.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CFAP410	NM_004928.3	MANE Select	c.707A>G	p.Gln236Arg	missense	Exon 7 of 7	NP_004919.1
CFAP410	NM_001271441.2		c.1064A>G	p.Gln355Arg	missense	Exon 7 of 7	NP_001258370.1
CFAP410	NM_001271440.2		c.704A>G	p.Gln235Arg	missense	Exon 7 of 7	NP_001258369.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CFAP410	ENST00000339818.9	TSL:1 MANE Select	c.707A>G	p.Gln236Arg	missense	Exon 7 of 7	ENSP00000344566.4
CFAP410	ENST00000397956.7	TSL:1	c.1064A>G	p.Gln355Arg	missense	Exon 7 of 7	ENSP00000381047.3
CFAP410	ENST00000325223.7	TSL:1	c.704A>G	p.Gln235Arg	missense	Exon 7 of 7	ENSP00000317302.7

Frequencies

GnomAD3 genomes

AF:

0.0934

AC:

14212

AN:

152212

Hom.:

743

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0505

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.135

Gnomad ASJ

AF:

0.0908

Gnomad EAS

AF:

0.0246

Gnomad SAS

AF:

0.113

Gnomad FIN

AF:

0.113

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.111

Gnomad OTH

AF:

0.113

GnomAD2 exomes

AF:

0.105

AC:

23288

AN:

220876

AF XY:

0.107

show subpopulations

Gnomad AFR exome

AF:

0.0471

Gnomad AMR exome

AF:

0.151

Gnomad ASJ exome

AF:

0.0839

Gnomad EAS exome

AF:

0.0238

Gnomad FIN exome

AF:

0.107

Gnomad NFE exome

AF:

0.113

Gnomad OTH exome

AF:

0.109

GnomAD4 exome

AF:

0.109

AC:

158192

AN:

1449832

Hom.:

9060

Cov.:

AF XY:

0.109

AC XY:

78808

AN XY:

720382

show subpopulations

African (AFR)

AF:

0.0447

AC:

1491

AN:

33356

American (AMR)

AF:

0.153

AC:

6657

AN:

43478

Ashkenazi Jewish (ASJ)

AF:

0.0862

AC:

2234

AN:

25902

East Asian (EAS)

AF:

0.0232

AC:

915

AN:

39372

South Asian (SAS)

AF:

0.110

AC:

9299

AN:

84684

European-Finnish (FIN)

AF:

0.109

AC:

5405

AN:

49400

Middle Eastern (MID)

AF:

0.104

AC:

597

AN:

5738

European-Non Finnish (NFE)

AF:

0.113

AC:

125491

AN:

1107982

Other (OTH)

AF:

0.102

AC:

6103

AN:

59920

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

8517

17034

25552

34069

42586

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4556

9112

13668

18224

22780

<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

AF:

0.0933

AC:

14212

AN:

152330

Hom.:

742

Cov.:

AF XY:

0.0936

AC XY:

6974

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.0504

AC:

2097

AN:

41576

American (AMR)

AF:

0.134

AC:

2058

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0908

AC:

315

AN:

3470

East Asian (EAS)

AF:

0.0249

AC:

129

AN:

5188

South Asian (SAS)

AF:

0.113

AC:

545

AN:

4832

European-Finnish (FIN)

AF:

0.113

AC:

1196

AN:

10622

Middle Eastern (MID)

AF:

0.129

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.111

AC:

7583

AN:

68020

Other (OTH)

AF:

0.111

AC:

235

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

708

1416

2125

2833

3541

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

328

492

656

820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.110

Hom.:

414

Bravo

AF:

0.0927

TwinsUK

AF:

0.107

AC:

397

ALSPAC

AF:

0.118

AC:

456

ESP6500AA

AF:

0.0440

AC:

192

ESP6500EA

AF:

0.110

AC:

939

ExAC

AF:

0.0967

AC:

11627

Asia WGS

AF:

0.0780

AC:

269

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

9.1

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.012

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.81

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.64

MetaRNN

Benign

0.0014

MetaSVM

Benign

-1.0

PhyloP100

3.1

PROVEAN

Benign

-1.6

REVEL

Benign

0.064

Sift

Benign

0.30

Sift4G

Benign

0.56

Polyphen

0.0030

Vest4

0.089

MPC

0.18

ClinPred

0.0037

GERP RS

2.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.063

gMVP

0.20

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over