rs920791

chr18-50250988-T-A

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.778-12A>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,607,288 control chromosomes in the GnomAD database, including 78,808 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (7799 hom., cov: 33)
  • Exomes 𝑓: 0.31 (71009 hom.)
• Consequence: CFAP53 NM_145020.5 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00002591
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.24

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=-0.8).
• BP6: Variant 18-50250988-T-A is Benign according to our data. Variant chr18-50250988-T-A is described in ClinVar as [Benign]. Clinvar id is 262557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP53	NM_145020.5	c.778-12A>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000398545.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP53	ENST00000398545.5	c.778-12A>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_145020.5	P1

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48215 AN: 151998 Hom.: 7785 Cov.: 33

Gnomad AFR AF: 0.364

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.316

Gnomad OTH AF: 0.295

GnomAD3 exomes AF: 0.293 AC: 72999 AN: 249256 Hom.: 11031 AF XY: 0.295 AC XY: 39837 AN XY: 135252

Gnomad AFR exome AF: 0.364

Gnomad AMR exome AF: 0.232

Gnomad ASJ exome AF: 0.267

Gnomad EAS exome AF: 0.204

Gnomad SAS exome AF: 0.309

Gnomad FIN exome AF: 0.315

Gnomad NFE exome AF: 0.310

Gnomad OTH exome AF: 0.288

GnomAD4 exome AF: 0.310 AC: 451598 AN: 1455172 Hom.: 71009 Cov.: 30 AF XY: 0.310 AC XY: 224600 AN XY: 724426

Gnomad4 AFR exome AF: 0.367

Gnomad4 AMR exome AF: 0.233

Gnomad4 ASJ exome AF: 0.264

Gnomad4 EAS exome AF: 0.246

Gnomad4 SAS exome AF: 0.305

Gnomad4 FIN exome AF: 0.316

Gnomad4 NFE exome AF: 0.315

Gnomad4 OTH exome AF: 0.310

GnomAD4 genome AF: 0.317 AC: 48264 AN: 152116 Hom.: 7799 Cov.: 33 AF XY: 0.315 AC XY: 23451 AN XY: 74366

Gnomad4 AFR AF: 0.364

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.260

Gnomad4 EAS AF: 0.211

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.315

Gnomad4 NFE AF: 0.316

Gnomad4 OTH AF: 0.299

Alfa AF: 0.314 Hom.: 1403

Bravo AF: 0.312

Asia WGS AF: 0.298 AC: 1035 AN: 3478

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

GeneDx

Jan 26, 2021

- -

Heterotaxy, visceral, 6, autosomal Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.32
Dann	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000026
dbscSNV1_RF	Benign	0.0
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: rs920791; hg19: chr18-47777358; COSMIC: COSV68353105;