NM_145020.5:c.1316+900T>C

Variant names:

• chr18-50237703-A-G
• rs768360
• NM_145020.5:c.1316+900T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145020.5(CFAP53):​c.1316+900T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 151,666 control chromosomes in the GnomAD database, including 8,546 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.33 (8546 hom., cov: 30)
• Consequence: CFAP53 NM_145020.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.871
• 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: Labcorp Genetics (formerly Invitae)
• situs inversus

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.421 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP53	NM_145020.5	MANE Select	c.1316+900T>C		intron	N/A	NP_659457.2	Q96M91

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP53	ENST00000398545.5	TSL:1 MANE Select	c.1316+900T>C		intron	N/A	ENSP00000381553.3	Q96M91
	CFAP53	ENST00000880606.1		c.1304+900T>C		intron	N/A	ENSP00000550665.1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49753 AN: 151548 Hom.: 8530 Cov.: 30

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.296

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.328 AC: 49809 AN: 151666 Hom.: 8546 Cov.: 30 AF XY: 0.326 AC XY: 24153 AN XY: 74048

African (AFR) AF: 0.426 AC: 17610 AN: 41300

American (AMR) AF: 0.256 AC: 3902 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 974 AN: 3470

East Asian (EAS) AF: 0.212 AC: 1091 AN: 5146

South Asian (SAS) AF: 0.306 AC: 1462 AN: 4782

European-Finnish (FIN) AF: 0.296 AC: 3113 AN: 10506

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

European-Non Finnish (NFE) AF: 0.305 AC: 20707 AN: 67910

Other (OTH) AF: 0.300 AC: 628 AN: 2096

Alfa AF: 0.316 Hom.: 1366

Bravo AF: 0.327

Asia WGS AF: 0.300 AC: 1043 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.90
DANN	Benign	0.30
PhyloP100		-0.87
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: rs768360; hg19: chr18-47764073;