Variant 18-50251567-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_145020.5(CFAP53):c.691C>T(p.Arg231Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0297 in 1,614,156 control chromosomes in the GnomAD database, including 7,342 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 869 hom., cov: 33)

Exomes 𝑓: 0.028 ( 6473 hom. )

Consequence

CFAP53
NM_145020.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.04

Variant links:

Genes affected

CFAP53 (HGNC:26530): (cilia and flagella associated protein 53) This gene belongs to the CFAP53 family. It was found to be differentially expressed by the ciliated cells of frog epidermis and in skin fibroblasts from human. Mutations in this gene are associated with visceral heterotaxy-6, which implicates this gene in determination of left-right asymmetric patterning. [provided by RefSeq, Aug 2015]

CFAP53 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031661391).

BP6

Variant 18-50251567-G-A is Benign according to our data. Variant chr18-50251567-G-A is described in ClinVar as [Benign]. Clinvar id is 262556.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP53	NM_145020.5 link	c.691C>T	p.Arg231Cys	missense_variant	Exon 4 of 8	ENST00000398545.5	NP_659457.2	Q96M91

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP53	ENST00000398545.5 link	c.691C>T	p.Arg231Cys	missense_variant	Exon 4 of 8	1	NM_145020.5	ENSP00000381553.3		Q96M91

Frequencies

GnomAD3 genomes

AF:

0.0410

AC:

6239

AN:

152170

Hom.:

863

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00596

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.169

Gnomad ASJ

AF:

0.0184

Gnomad EAS

AF:

0.446

Gnomad SAS

AF:

0.0655

Gnomad FIN

AF:

0.0360

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00370

Gnomad OTH

AF:

0.0454

GnomAD3 exomes

AF:

0.0835

AC:

20839

AN:

249570

Hom.:

3319

AF XY:

0.0726

AC XY:

9835

AN XY:

135406

show subpopulations

Gnomad AFR exome

AF:

0.00517

Gnomad AMR exome

AF:

0.272

Gnomad ASJ exome

AF:

0.0164

Gnomad EAS exome

AF:

0.448

Gnomad SAS exome

AF:

0.0529

Gnomad FIN exome

AF:

0.0334

Gnomad NFE exome

AF:

0.00416

Gnomad OTH exome

AF:

0.0551

GnomAD4 exome

AF:

0.0285

AC:

41629

AN:

1461868

Hom.:

6473

Cov.:

AF XY:

0.0280

AC XY:

20361

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00397

Gnomad4 AMR exome

AF:

0.258

Gnomad4 ASJ exome

AF:

0.0185

Gnomad4 EAS exome

AF:

0.470

Gnomad4 SAS exome

AF:

0.0544

Gnomad4 FIN exome

AF:

0.0334

Gnomad4 NFE exome

AF:

0.00182

Gnomad4 OTH exome

AF:

0.0372

GnomAD4 genome

AF:

0.0411

AC:

6255

AN:

152288

Hom.:

869

Cov.:

AF XY:

0.0478

AC XY:

3562

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00594

Gnomad4 AMR

AF:

0.169

Gnomad4 ASJ

AF:

0.0184

Gnomad4 EAS

AF:

0.446

Gnomad4 SAS

AF:

0.0661

Gnomad4 FIN

AF:

0.0360

Gnomad4 NFE

AF:

0.00370

Gnomad4 OTH

AF:

0.0459

Alfa

AF:

0.0254

Hom.:

1101

Bravo

AF:

0.0528

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.00486

AC:

ESP6500EA

AF:

0.00381

AC:

ExAC

AF:

0.0734

AC:

8885

Asia WGS

AF:

0.227

AC:

786

AN:

3478

EpiCase

AF:

0.00202

EpiControl

AF:

0.00202

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Heterotaxy, visceral, 6, autosomal

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2025

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.049

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.78

MetaRNN

Benign

0.0032

MetaSVM

Benign

-0.93

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.8

REVEL

Benign

0.13

Sift

Benign

0.044

Sift4G

Uncertain

0.0050

Polyphen

0.13

Vest4

0.24

MPC

0.43

ClinPred

0.022

GERP RS

1.3

Varity_R

0.087

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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