Variant 18-50250874-C-T 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.880G>A(p.Glu294Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 1,613,874 control chromosomes in the GnomAD database, including 104,227 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 7093 hom., cov: 33)

Exomes 𝑓: 0.35 ( 97134 hom. )

Consequence

CFAP53
NM_145020.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.98

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=0.003494829).

BP6

Variant 18-50250874-C-T is Benign according to our data. Variant chr18-50250874-C-T is described in ClinVar as [Benign]. Clinvar id is 262560.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-50250874-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP53	NM_145020.5 linkuse as main transcript	c.880G>A	p.Glu294Lys	missense_variant	5/8	ENST00000398545.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP53	ENST00000398545.5 linkuse as main transcript	c.880G>A	p.Glu294Lys	missense_variant	5/8	1	NM_145020.5	P1

Frequencies

GnomAD3 genomes

AF:

0.283

AC:

43077

AN:

152028

Hom.:

7095

Cov.:

show subpopulations

Gnomad AFR

AF:

0.136

Gnomad AMI

AF:

0.416

Gnomad AMR

AF:

0.240

Gnomad ASJ

AF:

0.344

Gnomad EAS

AF:

0.0582

Gnomad SAS

AF:

0.257

Gnomad FIN

AF:

0.389

Gnomad MID

AF:

0.354

Gnomad NFE

AF:

0.380

Gnomad OTH

AF:

0.308

GnomAD3 exomes

AF:

0.296

AC:

73917

AN:

249552

Hom.:

12755

AF XY:

0.304

AC XY:

41184

AN XY:

135388

show subpopulations

Gnomad AFR exome

AF:

0.132

Gnomad AMR exome

AF:

0.171

Gnomad ASJ exome

AF:

0.324

Gnomad EAS exome

AF:

0.0582

Gnomad SAS exome

AF:

0.264

Gnomad FIN exome

AF:

0.390

Gnomad NFE exome

AF:

0.381

Gnomad OTH exome

AF:

0.338

GnomAD4 exome

AF:

0.355

AC:

518359

AN:

1461728

Hom.:

97134

Cov.:

AF XY:

0.354

AC XY:

257196

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.124

Gnomad4 AMR exome

AF:

0.180

Gnomad4 ASJ exome

AF:

0.329

Gnomad4 EAS exome

AF:

0.0514

Gnomad4 SAS exome

AF:

0.269

Gnomad4 FIN exome

AF:

0.393

Gnomad4 NFE exome

AF:

0.386

Gnomad4 OTH exome

AF:

0.331

GnomAD4 genome

AF:

0.283

AC:

43072

AN:

152146

Hom.:

7093

Cov.:

AF XY:

0.282

AC XY:

20939

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.136

Gnomad4 AMR

AF:

0.239

Gnomad4 ASJ

AF:

0.344

Gnomad4 EAS

AF:

0.0582

Gnomad4 SAS

AF:

0.257

Gnomad4 FIN

AF:

0.389

Gnomad4 NFE

AF:

0.380

Gnomad4 OTH

AF:

0.304

Alfa

AF:

0.347

Hom.:

15642

Bravo

AF:

0.263

TwinsUK

AF:

0.393

AC:

1458

ALSPAC

AF:

0.380

AC:

1465

ESP6500AA

AF:

0.144

AC:

542

ESP6500EA

AF:

0.378

AC:

3112

ExAC

AF:

0.300

AC:

36269

Asia WGS

AF:

0.155

AC:

542

AN:

3478

EpiCase

AF:

0.382

EpiControl

AF:

0.389

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 26, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Heterotaxy, visceral, 6, autosomal

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.013

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.78

MetaRNN

Benign

0.0035

MetaSVM

Benign

-0.94

MutationTaster

Benign

1.0

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.1

REVEL

Benign

0.089

Sift

Benign

0.18

Sift4G

Uncertain

0.046

Polyphen

0.58

Vest4

0.064

MPC

0.10

ClinPred

0.012

GERP RS

4.9

Varity_R

0.091

gMVP

0.17

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