Variant 21-44330229-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 2P and 14B. PM1BP4_StrongBP6_ModerateBS1BS2

The NM_004928.3(CFAP410):c.740G>A(p.Arg247His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000351 in 1,585,248 control chromosomes in the GnomAD database, including 9 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 0.00064 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00032 ( 6 hom. )

Consequence

CFAP410
NM_004928.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.152

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:

CFAP410 (HGNC:):

CFAP410 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 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=0.0023603141).

BP6

Variant 21-44330229-C-T is Benign according to our data. Variant chr21-44330229-C-T is described in ClinVar as [Benign]. Clinvar id is 716898.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr21-44330229-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000643 (98/152344) while in subpopulation EAS AF= 0.0152 (79/5188). AF 95% confidence interval is 0.0125. There are 3 homozygotes in gnomad4. There are 54 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP410	NM_004928.3 linkuse as main transcript	c.740G>A	p.Arg247His	missense_variant	7/7	ENST00000339818.9	NP_004919.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP410	ENST00000339818.9 linkuse as main transcript	c.740G>A	p.Arg247His	missense_variant	7/7	1	NM_004928.3	ENSP00000344566.4		O43822-1

Frequencies

GnomAD3 genomes

AF:

0.000644

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0152

Gnomad SAS

AF:

0.00289

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00121

AC:

238

AN:

197044

Hom.:

AF XY:

0.00111

AC XY:

120

AN XY:

107998

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0145

Gnomad SAS exome

AF:

0.000414

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000118

Gnomad OTH exome

AF:

0.00117

GnomAD4 exome

AF:

0.000320

AC:

459

AN:

1432904

Hom.:

Cov.:

AF XY:

0.000319

AC XY:

227

AN XY:

710854

show subpopulations

Gnomad4 AFR exome

AF:

0.0000302

Gnomad4 AMR exome

AF:

0.0000242

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00764

Gnomad4 SAS exome

AF:

0.000700

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000291

Gnomad4 OTH exome

AF:

0.00123

GnomAD4 genome

AF:

0.000643

AC:

AN:

152344

Hom.:

Cov.:

AF XY:

0.000725

AC XY:

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0152

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000624

Hom.:

Bravo

AF:

0.000691

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.000982

AC:

118

Asia WGS

AF:

0.00664

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 26, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.67

CADD

Benign

8.4

DANN

Benign

0.83

DEOGEN2

Benign

0.0030

T;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.78

T;T;T

MetaRNN

Benign

0.0024

T;T;T

MetaSVM

Benign

-1.0

PROVEAN

Benign

0.69

N;N;N

REVEL

Benign

0.014

Sift

Benign

0.61

T;T;T

Sift4G

Benign

0.37

T;T;T

Polyphen

0.0010

B;.;.

Vest4

0.076

MVP

0.15

MPC

0.37

ClinPred

0.020

GERP RS

1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.021

gMVP

0.029

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