Variant 18-50250815-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_145020.5(CFAP53):c.939C>T(p.Leu313Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00178 in 1,614,148 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0090 ( 20 hom., cov: 33)

Exomes 𝑓: 0.0010 ( 22 hom. )

Consequence

CFAP53
NM_145020.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.59

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 18-50250815-G-A is Benign according to our data. Variant chr18-50250815-G-A is described in ClinVar as [Benign]. Clinvar id is 262561.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.59 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00905 (1378/152266) while in subpopulation AFR AF= 0.0306 (1271/41532). AF 95% confidence interval is 0.0292. There are 20 homozygotes in gnomad4. There are 626 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP53	NM_145020.5 link	c.939C>T	p.Leu313Leu	synonymous_variant	5/8	ENST00000398545.5	NP_659457.2	Q96M91

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP53	ENST00000398545.5 link	c.939C>T	p.Leu313Leu	synonymous_variant	5/8	1	NM_145020.5	ENSP00000381553.3		Q96M91

Frequencies

GnomAD3 genomes

AF:

0.00898

AC:

1367

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0304

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00530

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00243

AC:

607

AN:

249562

Hom.:

AF XY:

0.00179

AC XY:

243

AN XY:

135396

show subpopulations

Gnomad AFR exome

AF:

0.0312

Gnomad AMR exome

AF:

0.00232

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000159

Gnomad OTH exome

AF:

0.00132

GnomAD4 exome

AF:

0.00102

AC:

1498

AN:

1461882

Hom.:

Cov.:

AF XY:

0.000887

AC XY:

645

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0298

Gnomad4 AMR exome

AF:

0.00273

Gnomad4 ASJ exome

AF:

0.00168

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.0000749

Gnomad4 NFE exome

AF:

0.000144

Gnomad4 OTH exome

AF:

0.00248

GnomAD4 genome

AF:

0.00905

AC:

1378

AN:

152266

Hom.:

Cov.:

AF XY:

0.00841

AC XY:

626

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0306

Gnomad4 AMR

AF:

0.00523

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00378

Hom.:

Bravo

AF:

0.0106

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000327

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

Jan 12, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.27

DANN

Benign

0.63

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