chr18-50250988-T-A

Variant names:

• chr18-50250988-T-A
• rs920791
• NM_145020.5:c.778-12A>T

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.778-12A>T variant causes a 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 intron
• Scores: Splicing: ADA: 0.00002591
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -2.24
• Publications: 6 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=-0.8).
• BP6: Variant 18-50250988-T-A is Benign according to our data. Variant chr18-50250988-T-A is described in ClinVar as Benign. ClinVar VariationId 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 rank	MANE	Protein	UniProt
CFAP53	NM_145020.5	c.778-12A>T		intron_variant	Intron 4 of 7	ENST00000398545.5	NP_659457.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP53	ENST00000398545.5	c.778-12A>T		intron_variant	Intron 4 of 7	1	NM_145020.5	ENSP00000381553.3

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

GnomAD2 exomes AF: 0.293 AC: 72999 AN: 249256 AF XY: 0.295

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 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

African (AFR) AF: 0.367 AC: 12241 AN: 33342

American (AMR) AF: 0.233 AC: 10393 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 6874 AN: 26086

East Asian (EAS) AF: 0.246 AC: 9775 AN: 39668

South Asian (SAS) AF: 0.305 AC: 26221 AN: 86076

European-Finnish (FIN) AF: 0.316 AC: 16819 AN: 53208

Middle Eastern (MID) AF: 0.282 AC: 1553 AN: 5504

European-Non Finnish (NFE) AF: 0.315 AC: 349052 AN: 1106442

Other (OTH) AF: 0.310 AC: 18670 AN: 60150

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

African (AFR) AF: 0.364 AC: 15113 AN: 41494

American (AMR) AF: 0.257 AC: 3926 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 902 AN: 3472

East Asian (EAS) AF: 0.211 AC: 1092 AN: 5170

South Asian (SAS) AF: 0.307 AC: 1482 AN: 4826

European-Finnish (FIN) AF: 0.315 AC: 3331 AN: 10564

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.316 AC: 21465 AN: 67992

Other (OTH) AF: 0.299 AC: 632 AN: 2112

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:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jan 26, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Heterotaxy, visceral, 6, autosomal Benign:1

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.32
DANN	Benign	0.43
PhyloP100		-2.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs920791; hg19: chr18-47777358; COSMIC: COSV68353105;