Variant 18-50251643-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_145020.5(CFAP53):c.615G>C(p.Trp205Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00119 in 1,614,200 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0064 ( 7 hom., cov: 33)

Exomes 𝑓: 0.00064 ( 8 hom. )

Consequence

CFAP53
NM_145020.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.94

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=0.008304417).

BP6

Variant 18-50251643-C-G is Benign according to our data. Variant chr18-50251643-C-G is described in ClinVar as [Benign]. Clinvar id is 262555.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00638 (971/152308) while in subpopulation AFR AF= 0.0221 (917/41562). AF 95% confidence interval is 0.0209. There are 7 homozygotes in gnomad4. There are 492 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP53	NM_145020.5 linkuse as main transcript	c.615G>C	p.Trp205Cys	missense_variant	4/8	ENST00000398545.5	NP_659457.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP53	ENST00000398545.5 linkuse as main transcript	c.615G>C	p.Trp205Cys	missense_variant	4/8	1	NM_145020.5	ENSP00000381553	P1

Frequencies

GnomAD3 genomes

AF:

0.00637

AC:

970

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0221

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00164

AC:

409

AN:

249582

Hom.:

AF XY:

0.00143

AC XY:

193

AN XY:

135406

show subpopulations

Gnomad AFR exome

AF:

0.0220

Gnomad AMR exome

AF:

0.00119

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000177

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.000644

AC:

942

AN:

1461892

Hom.:

Cov.:

AF XY:

0.000569

AC XY:

414

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0199

Gnomad4 AMR exome

AF:

0.00145

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000944

Gnomad4 OTH exome

AF:

0.00147

GnomAD4 genome

AF:

0.00638

AC:

971

AN:

152308

Hom.:

Cov.:

AF XY:

0.00661

AC XY:

492

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0221

Gnomad4 AMR

AF:

0.00190

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000220

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.000988

Hom.:

Bravo

AF:

0.00677

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0146

AC:

ESP6500EA

AF:

0.000359

AC:

ExAC

AF:

0.00206

AC:

249

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000356

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

Oct 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.83

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.36

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.081

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.85

MetaRNN

Benign

0.0083

MetaSVM

Benign

-1.2

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.55

PROVEAN

Pathogenic

-7.8

REVEL

Benign

0.19

Sift

Uncertain

0.0010

Sift4G

Benign

0.080

Polyphen

1.0

Vest4

0.43

MutPred

0.27

Loss of MoRF binding (P = 0.0263);

MVP

0.34

MPC

0.47

ClinPred

0.047

GERP RS

5.3

Varity_R

0.81

gMVP

0.25

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