rs2277809

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.449C>T(p.Thr150Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0288 in 1,613,518 control chromosomes in the GnomAD database, including 912 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 (★★). Synonymous variant affecting the same amino acid position (i.e. T150T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.021 ( 51 hom., cov: 33)

Exomes 𝑓: 0.030 ( 861 hom. )

Consequence

CFAP410
NM_004928.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.599

Publications

21 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:

ENSG00000184441 (HGNC:):

ENSG00000184441 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=0.0021091402).

BP6

Variant 21-44331939-G-A is Benign according to our data. Variant chr21-44331939-G-A is described in ClinVar as Benign. ClinVar VariationId is 259587.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP410	NM_004928.3 link	c.449C>T	p.Thr150Ile	missense_variant	Exon 5 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.449C>T	p.Thr150Ile	missense_variant	Exon 5 of 7	1	NM_004928.3	ENSP00000344566.4		O43822-1

Frequencies

GnomAD3 genomes

AF:

0.0211

AC:

3211

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00753

Gnomad AMI

AF:

0.0658

Gnomad AMR

AF:

0.0184

Gnomad ASJ

AF:

0.0311

Gnomad EAS

AF:

0.0544

Gnomad SAS

AF:

0.0715

Gnomad FIN

AF:

0.00743

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0247

Gnomad OTH

AF:

0.0239

GnomAD2 exomes

AF:

0.0290

AC:

7244

AN:

249586

AF XY:

0.0316

show subpopulations

Gnomad AFR exome

AF:

0.00633

Gnomad AMR exome

AF:

0.0161

Gnomad ASJ exome

AF:

0.0361

Gnomad EAS exome

AF:

0.0573

Gnomad FIN exome

AF:

0.00850

Gnomad NFE exome

AF:

0.0246

Gnomad OTH exome

AF:

0.0294

GnomAD4 exome

AF:

0.0296

AC:

43279

AN:

1461156

Hom.:

861

Cov.:

AF XY:

0.0310

AC XY:

22556

AN XY:

726844

show subpopulations

African (AFR)

AF:

0.00574

AC:

192

AN:

33464

American (AMR)

AF:

0.0160

AC:

715

AN:

44662

Ashkenazi Jewish (ASJ)

AF:

0.0358

AC:

936

AN:

26128

East Asian (EAS)

AF:

0.0640

AC:

2538

AN:

39674

South Asian (SAS)

AF:

0.0662

AC:

5708

AN:

86196

European-Finnish (FIN)

AF:

0.00870

AC:

462

AN:

53108

Middle Eastern (MID)

AF:

0.0397

AC:

229

AN:

5766

European-Non Finnish (NFE)

AF:

0.0275

AC:

30556

AN:

1111782

Other (OTH)

AF:

0.0322

AC:

1943

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

2222

4444

6666

8888

11110

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1260

2520

3780

5040

6300

<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:

0.0211

AC:

3210

AN:

152362

Hom.:

Cov.:

AF XY:

0.0211

AC XY:

1570

AN XY:

74508

show subpopulations

African (AFR)

AF:

0.00750

AC:

312

AN:

41580

American (AMR)

AF:

0.0184

AC:

282

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.0311

AC:

108

AN:

3470

East Asian (EAS)

AF:

0.0544

AC:

282

AN:

5188

South Asian (SAS)

AF:

0.0718

AC:

347

AN:

4832

European-Finnish (FIN)

AF:

0.00743

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0247

AC:

1680

AN:

68030

Other (OTH)

AF:

0.0236

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

163

326

489

652

815

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<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:

0.0260

Hom.:

252

Bravo

AF:

0.0211

TwinsUK

AF:

0.0334

AC:

124

ALSPAC

AF:

0.0267

AC:

103

ESP6500AA

AF:

0.00976

AC:

ESP6500EA

AF:

0.0280

AC:

241

ExAC

AF:

0.0295

AC:

3575

Asia WGS

AF:

0.0490

AC:

171

AN:

3478

EpiCase

AF:

0.0304

EpiControl

AF:

0.0299

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

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

- -

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

0.10

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.64

CADD

Benign

1.8

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.014

T;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.65

T;T;T

MetaRNN

Benign

0.0021

T;T;T

MetaSVM

Benign

-1.1

PhyloP100

0.60

PROVEAN

Benign

-1.6

N;N;N

REVEL

Benign

0.096

Sift

Benign

0.43

T;T;T

Sift4G

Benign

0.25

T;T;T

Polyphen

0.54

P;.;.

Vest4

0.080

MPC

0.11

ClinPred

0.0058

GERP RS

-3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.032

gMVP

0.23

Mutation Taster

=97/3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over