dbSNP rs920791: CFAP53:c.778-12A>T (chr18-50250988-T-A) – ACMG Classification: Benign (-20 pts)

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.778-12A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,607,288 control chromosomes in the GnomAD database, including 78,808 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 7799 hom., cov: 33)

Exomes 𝑓: 0.31 ( 71009 hom. )

Consequence

CFAP53
NM_145020.5 intron

Scores

Splicing: ADA: 0.00002591

Clinical Significance

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

Conservation

PhyloP100: -2.24

Publications

6 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 (BayesDel_noAF=-0.8).

BP6

Variant 18-50250988-T-A is Benign according to our data. Variant chr18-50250988-T-A is described in ClinVar as Benign. ClinVar VariationId is 262557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP53	NM_145020.5 link	c.778-12A>T		intron_variant	Intron 4 of 7	ENST00000398545.5	NP_659457.2	Q96M91

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP53	ENST00000398545.5 link	c.778-12A>T		intron_variant	Intron 4 of 7	1	NM_145020.5	ENSP00000381553.3		Q96M91

Frequencies

GnomAD3 genomes

AF:

0.317

AC:

48215

AN:

151998

Hom.:

7785

Cov.:

show subpopulations

Gnomad AFR

AF:

0.364

Gnomad AMI

AF:

0.246

Gnomad AMR

AF:

0.257

Gnomad ASJ

AF:

0.260

Gnomad EAS

AF:

0.211

Gnomad SAS

AF:

0.308

Gnomad FIN

AF:

0.315

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.316

Gnomad OTH

AF:

0.295

GnomAD2 exomes

AF:

0.293

AC:

72999

AN:

249256

AF XY:

0.295

show subpopulations

Gnomad AFR exome

AF:

0.364

Gnomad AMR exome

AF:

0.232

Gnomad ASJ exome

AF:

0.267

Gnomad EAS exome

AF:

0.204

Gnomad FIN exome

AF:

0.315

Gnomad NFE exome

AF:

0.310

Gnomad OTH exome

AF:

0.288

GnomAD4 exome

AF:

0.310

AC:

451598

AN:

1455172

Hom.:

71009

Cov.:

AF XY:

0.310

AC XY:

224600

AN XY:

724426

show subpopulations

African (AFR)

AF:

0.367

AC:

12241

AN:

33342

American (AMR)

AF:

0.233

AC:

10393

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.264

AC:

6874

AN:

26086

East Asian (EAS)

AF:

0.246

AC:

9775

AN:

39668

South Asian (SAS)

AF:

0.305

AC:

26221

AN:

86076

European-Finnish (FIN)

AF:

0.316

AC:

16819

AN:

53208

Middle Eastern (MID)

AF:

0.282

AC:

1553

AN:

5504

European-Non Finnish (NFE)

AF:

0.315

AC:

349052

AN:

1106442

Other (OTH)

AF:

0.310

AC:

18670

AN:

60150

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

16929

33858

50787

67716

84645

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11360

22720

34080

45440

56800

<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:

0.317

AC:

48264

AN:

152116

Hom.:

7799

Cov.:

AF XY:

0.315

AC XY:

23451

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.364

AC:

15113

AN:

41494

American (AMR)

AF:

0.257

AC:

3926

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.260

AC:

902

AN:

3472

East Asian (EAS)

AF:

0.211

AC:

1092

AN:

5170

South Asian (SAS)

AF:

0.307

AC:

1482

AN:

4826

European-Finnish (FIN)

AF:

0.315

AC:

3331

AN:

10564

Middle Eastern (MID)

AF:

0.330

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.316

AC:

21465

AN:

67992

Other (OTH)

AF:

0.299

AC:

632

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1676

3352

5028

6704

8380

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

504

1008

1512

2016

2520

<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:

0.314

Hom.:

1403

Bravo

AF:

0.312

Asia WGS

AF:

0.298

AC:

1035

AN:

3478

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

Jan 29, 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

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.32

(source)

DANN

Benign

0.43

PhyloP100

-2.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000026

dbscSNV1_RF

Benign

0.0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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