rs114015053

chr18-50250965-G-Achr18-50250965-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_145020.5(CFAP53):c.789C>T(p.Asn263=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000788 in 1,613,530 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0040 (4 hom., cov: 33)
  • Exomes 𝑓: 0.00046 (4 hom.)
• Consequence: CFAP53 NM_145020.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.849

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 18-50250965-G-A is Benign according to our data. Variant chr18-50250965-G-A is described in ClinVar as [Benign]. Clinvar id is 262558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-50250965-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.849 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00399 (607/152190) while in subpopulation AFR AF= 0.0137 (567/41504). AF 95% confidence interval is 0.0127. There are 4 homozygotes in gnomad4. There are 298 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP53	NM_145020.5	c.789C>T	p.Asn263=	synonymous_variant	5/8	ENST00000398545.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP53	ENST00000398545.5	c.789C>T	p.Asn263=	synonymous_variant	5/8	1	NM_145020.5	P1

Frequencies

GnomAD3 genomes AF: 0.00398 AC: 606 AN: 152072 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.0137

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.000930 AC: 232 AN: 249418 Hom.: 0 AF XY: 0.000761 AC XY: 103 AN XY: 135328

Gnomad AFR exome AF: 0.0123

Gnomad AMR exome AF: 0.000550

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000159

Gnomad OTH exome AF: 0.000330

GnomAD4 exome AF: 0.000455 AC: 665 AN: 1461340 Hom.: 4 Cov.: 33 AF XY: 0.000409 AC XY: 297 AN XY: 727004

Gnomad4 AFR exome AF: 0.0149

Gnomad4 AMR exome AF: 0.000447

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000928

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000441

Gnomad4 OTH exome AF: 0.00114

GnomAD4 genome AF: 0.00399 AC: 607 AN: 152190 Hom.: 4 Cov.: 33 AF XY: 0.00401 AC XY: 298 AN XY: 74398

Gnomad4 AFR AF: 0.0137

Gnomad4 AMR AF: 0.00164

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00109 Hom.: 0

Bravo AF: 0.00441

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

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

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

CFAP53: BP4, BP7, BS1, BS2 -

Heterotaxy, visceral, 6, autosomal Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 10, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.4
Dann	Benign	0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

Other links and lift over

dbSNP: rs114015053; hg19: chr18-47777335;