Variant 10-132808600-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001200049.3(CFAP46):c.7969C>T(p.Arg2657Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00199 in 1,612,436 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0020 ( 8 hom. )

Consequence

CFAP46
NM_001200049.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.45

Variant links:

Genes affected

CFAP46 (HGNC:25247): (cilia and flagella associated protein 46) Predicted to be involved in axoneme assembly. Predicted to be located in axoneme. [provided by Alliance of Genome Resources, Apr 2022]

CFAP46 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0055638254).

BP6

Variant 10-132808600-G-A is Benign according to our data. Variant chr10-132808600-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3027413.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP46	NM_001200049.3 linkuse as main transcript	c.7969C>T	p.Arg2657Cys	missense_variant	58/58	ENST00000368586.10	NP_001186978.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP46	ENST00000368586.10 linkuse as main transcript	c.7969C>T	p.Arg2657Cys	missense_variant	58/58	5	NM_001200049.3	ENSP00000357575	A2	Q8IYW2-1
CFAP46	ENST00000639072.2 linkuse as main transcript	c.*192C>T		3_prime_UTR_variant	59/59	5		ENSP00000491877	P3

Frequencies

GnomAD3 genomes

AF:

0.00167

AC:

254

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.000658

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00309

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00158

AC:

385

AN:

243676

Hom.:

AF XY:

0.00165

AC XY:

220

AN XY:

132954

show subpopulations

Gnomad AFR exome

AF:

0.000327

Gnomad AMR exome

AF:

0.000813

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00209

Gnomad FIN exome

AF:

0.000511

Gnomad NFE exome

AF:

0.00247

Gnomad OTH exome

AF:

0.00183

GnomAD4 exome

AF:

0.00202

AC:

2955

AN:

1460140

Hom.:

Cov.:

AF XY:

0.00201

AC XY:

1461

AN XY:

726390

show subpopulations

Gnomad4 AFR exome

AF:

0.000418

Gnomad4 AMR exome

AF:

0.000895

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00188

Gnomad4 FIN exome

AF:

0.000785

Gnomad4 NFE exome

AF:

0.00234

Gnomad4 OTH exome

AF:

0.00123

GnomAD4 genome

AF:

0.00167

AC:

254

AN:

152296

Hom.:

Cov.:

AF XY:

0.00161

AC XY:

120

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.000658

Gnomad4 NFE

AF:

0.00309

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00177

Hom.:

Bravo

AF:

0.00133

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.00175

AC:

ExAC

AF:

0.00164

AC:

199

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

CFAP46: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.69

CADD

Benign

3.9

DANN

Benign

0.70

DEOGEN2

Benign

0.0082

Eigen

Benign

-2.2

Eigen_PC

Benign

-2.3

FATHMM_MKL

Benign

0.0021

LIST_S2

Benign

0.46

M_CAP

Benign

0.0056

MetaRNN

Benign

0.0056

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.17

REVEL

Benign

0.0070

Sift

Pathogenic

0.0

Sift4G

Benign

0.11

Vest4

0.14

MVP

0.014

MPC

0.15

ClinPred

0.0053

GERP RS

-3.5

Varity_R

0.084

gMVP

0.043

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