chr18-50251802-A-G

Variant names:

• chr18-50251802-A-G
• rs35295154
• NM_145020.5:c.474-18T>C

Variant summary

Our verdict is Benign. The variant received -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:3
• Conservation: PhyloP100: 2.28
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• heterotaxy, visceral, 6, autosomal

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• situs inversus

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 262553.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145020.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP53	NM_145020.5	MANE Select	c.474-18T>C		intron	N/A	NP_659457.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP53	ENST00000398545.5	TSL:1 MANE Select	c.474-18T>C		intron	N/A	ENSP00000381553.3

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

GnomAD2 exomes AF: 0.313 AC: 76977 AN: 246316 AF XY: 0.321

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 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

African (AFR) AF: 0.127 AC: 4216 AN: 33176

American (AMR) AF: 0.190 AC: 8412 AN: 44210

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 9125 AN: 25960

East Asian (EAS) AF: 0.0515 AC: 2041 AN: 39646

South Asian (SAS) AF: 0.276 AC: 23662 AN: 85878

European-Finnish (FIN) AF: 0.425 AC: 22232 AN: 52264

Middle Eastern (MID) AF: 0.332 AC: 1909 AN: 5748

European-Non Finnish (NFE) AF: 0.412 AC: 456480 AN: 1107212

Other (OTH) AF: 0.351 AC: 21077 AN: 60042

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

African (AFR) AF: 0.140 AC: 5835 AN: 41532

American (AMR) AF: 0.248 AC: 3796 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 1284 AN: 3470

East Asian (EAS) AF: 0.0581 AC: 301 AN: 5182

South Asian (SAS) AF: 0.262 AC: 1263 AN: 4818

European-Finnish (FIN) AF: 0.426 AC: 4494 AN: 10550

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.402 AC: 27299 AN: 67970

Other (OTH) AF: 0.321 AC: 677 AN: 2110

Alfa AF: 0.351 Hom.: 3278

Bravo AF: 0.277

Asia WGS AF: 0.158 AC: 550 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Heterotaxy, visceral, 6, autosomal Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.8
DANN	Benign	0.62
PhyloP100		2.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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