rs35295154

chr18-50251802-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_145020.5(CFAP53):c.474-18T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 1,606,260 control chromosomes in the GnomAD database, including 118,020 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7959 hom., cov: 33)
  • Exomes 𝑓: 0.38 (110061 hom.)
• Consequence: CFAP53 NM_145020.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.28

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 18-50251802-A-G is Benign according to our data. Variant chr18-50251802-A-G is described in ClinVar as [Benign]. Clinvar id is 262553.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-50251802-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP53	NM_145020.5	c.474-18T>C		intron_variant		ENST00000398545.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP53	ENST00000398545.5	c.474-18T>C		intron_variant		1	NM_145020.5	P1

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45430 AN: 152006 Hom.: 7961 Cov.: 33

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.0581

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.426

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.325

GnomAD3 exomes AF: 0.313 AC: 76977 AN: 246316 Hom.: 14069 AF XY: 0.321 AC XY: 42913 AN XY: 133766

Gnomad AFR exome AF: 0.137

Gnomad AMR exome AF: 0.180

Gnomad ASJ exome AF: 0.348

Gnomad EAS exome AF: 0.0587

Gnomad SAS exome AF: 0.270

Gnomad FIN exome AF: 0.425

Gnomad NFE exome AF: 0.403

Gnomad OTH exome AF: 0.355

GnomAD4 exome AF: 0.378 AC: 549154 AN: 1454136 Hom.: 110061 Cov.: 32 AF XY: 0.376 AC XY: 271984 AN XY: 722980

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.190

Gnomad4 ASJ exome AF: 0.352

Gnomad4 EAS exome AF: 0.0515

Gnomad4 SAS exome AF: 0.276

Gnomad4 FIN exome AF: 0.425

Gnomad4 NFE exome AF: 0.412

Gnomad4 OTH exome AF: 0.351

GnomAD4 genome AF: 0.299 AC: 45425 AN: 152124 Hom.: 7959 Cov.: 33 AF XY: 0.297 AC XY: 22069 AN XY: 74356

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.370

Gnomad4 EAS AF: 0.0581

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.426

Gnomad4 NFE AF: 0.402

Gnomad4 OTH AF: 0.321

Alfa AF: 0.346 Hom.: 1811

Bravo AF: 0.277

Asia WGS AF: 0.158 AC: 550 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

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- -

Heterotaxy, visceral, 6, autosomal Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	8.8
Dann	Benign	0.62

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: rs35295154; hg19: chr18-47778172; COSMIC: COSV68352018; COSMIC: COSV68352018;