rs112087763

Positions:

• chr18-50262174-T-G

Variant summary

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

The ENST00000398545.5(CFAP53):​c.115A>C​(p.Arg39=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00397 in 1,614,224 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. R39R) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0040 (18 hom.)
• Consequence: CFAP53 ENST00000398545.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 1.11

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 18-50262174-T-G is Benign according to our data. Variant chr18-50262174-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 262550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.11 with no splicing effect.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00333 (507/152348) while in subpopulation SAS AF= 0.00456 (22/4826). AF 95% confidence interval is 0.00362. There are 0 homozygotes in gnomad4. There are 267 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP53	NM_145020.5	c.115A>C	p.Arg39=	synonymous_variant	2/8	ENST00000398545.5	NP_659457.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP53	ENST00000398545.5	c.115A>C	p.Arg39=	synonymous_variant	2/8	1	NM_145020.5	ENSP00000381553	P1

Frequencies

GnomAD3 genomes AF: 0.00332 AC: 505 AN: 152230 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00414

Gnomad FIN AF: 0.0153

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00401

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00389 AC: 972 AN: 249560 Hom.: 7 AF XY: 0.00411 AC XY: 556 AN XY: 135394

Gnomad AFR exome AF: 0.000387

Gnomad AMR exome AF: 0.000695

Gnomad ASJ exome AF: 0.00258

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00359

Gnomad FIN exome AF: 0.0132

Gnomad NFE exome AF: 0.00431

Gnomad OTH exome AF: 0.00561

GnomAD4 exome AF: 0.00404 AC: 5906 AN: 1461876 Hom.: 18 Cov.: 31 AF XY: 0.00410 AC XY: 2979 AN XY: 727238

Gnomad4 AFR exome AF: 0.000478

Gnomad4 AMR exome AF: 0.000827

Gnomad4 ASJ exome AF: 0.00260

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00393

Gnomad4 FIN exome AF: 0.0138

Gnomad4 NFE exome AF: 0.00405

Gnomad4 OTH exome AF: 0.00303

GnomAD4 genome AF: 0.00333 AC: 507 AN: 152348 Hom.: 0 Cov.: 32 AF XY: 0.00358 AC XY: 267 AN XY: 74506

Gnomad4 AFR AF: 0.000553

Gnomad4 AMR AF: 0.000915

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00456

Gnomad4 FIN AF: 0.0153

Gnomad4 NFE AF: 0.00401

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00405 Hom.: 2

Bravo AF: 0.00220

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00409

EpiControl AF: 0.00356

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2024	CFAP53: BP4, BP7 -

not specified Benign:2

Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

Heterotaxy, visceral, 6, autosomal Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 13, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.7
DANN	Benign	0.60

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

Other links and lift over

dbSNP: rs112087763; hg19: chr18-47788544;