18-50250874-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 13/20 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

Publications

28 publications found

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 Gene-Disease associations (from GenCC):

heterotaxy, visceral, 6, autosomal
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
situs inversus
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CFAP53 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=0.003494829).

BP6

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

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 rank	MANE	Protein	UniProt
CFAP53	NM_145020.5 link	c.880G>A	p.Glu294Lys	missense_variant	Exon 5 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.880G>A	p.Glu294Lys	missense_variant	Exon 5 of 8	1	NM_145020.5	ENSP00000381553.3		Q96M91

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

GnomAD2 exomes

AF:

0.296

AC:

73917

AN:

249552

AF XY:

0.304

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 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

African (AFR)

AF:

0.124

AC:

4151

AN:

33476

American (AMR)

AF:

0.180

AC:

8057

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.329

AC:

8599

AN:

26134

East Asian (EAS)

AF:

0.0514

AC:

2039

AN:

39698

South Asian (SAS)

AF:

0.269

AC:

23182

AN:

86252

European-Finnish (FIN)

AF:

0.393

AC:

20972

AN:

53420

Middle Eastern (MID)

AF:

0.328

AC:

1889

AN:

5766

European-Non Finnish (NFE)

AF:

0.386

AC:

429482

AN:

1111874

Other (OTH)

AF:

0.331

AC:

19988

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

19019

38038

57058

76077

95096

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13132

26264

39396

52528

65660

<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:

0.283

AC:

43072

AN:

152146

Hom.:

7093

Cov.:

AF XY:

0.282

AC XY:

20939

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.136

AC:

5655

AN:

41530

American (AMR)

AF:

0.239

AC:

3655

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.344

AC:

1193

AN:

3464

East Asian (EAS)

AF:

0.0582

AC:

302

AN:

5192

South Asian (SAS)

AF:

0.257

AC:

1238

AN:

4824

European-Finnish (FIN)

AF:

0.389

AC:

4114

AN:

10566

Middle Eastern (MID)

AF:

0.333

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.380

AC:

25797

AN:

67976

Other (OTH)

AF:

0.304

AC:

641

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1533

3066

4598

6131

7664

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

432

864

1296

1728

2160

<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:

0.333

Hom.:

20258

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

Jan 26, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Heterotaxy, visceral, 6, autosomal

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

0.092

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

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

PhyloP100

2.0

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

Mutation Taster

=100/0

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