rs17375557

Variant names:

• chr12-96524751-C-T
• rs17375557
• NM_001306084.2:c.1159-2495C>T

Variant summary

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

The NM_001306084.2(CFAP54):​c.1159-2495C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.092 in 152,224 control chromosomes in the GnomAD database, including 804 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 0.092 (804 hom., cov: 32)
• Consequence: CFAP54 NM_001306084.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.321
• Publications: 2 publications found

Genes affected

CFAP54 (HGNC:26456): (cilia and flagella associated protein 54) Predicted to be involved in cilium assembly; cilium movement involved in cell motility; and spermatogenesis. Predicted to act upstream of or within cerebrospinal fluid circulation; motile cilium assembly; and mucociliary clearance. Predicted to be located in axoneme. [provided by Alliance of Genome Resources, Apr 2022]

CFAP54 Gene-Disease associations (from GenCC):

• ciliary dyskinesia, primary, 54

  Inheritance: AR Classification: STRONG Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001306084.2. 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
	CFAP54	NM_001306084.2	MANE Select	c.1159-2495C>T		intron	N/A	NP_001293013.1	Q96N23-1
	CFAP54	NM_001367885.1		c.1159-2495C>T		intron	N/A	NP_001354814.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CFAP54	ENST00000524981.9	TSL:5 MANE Select	c.1159-2495C>T		intron	N/A	ENSP00000431759.5	Q96N23-1
	CFAP54	ENST00000553778.6	TSL:1	n.1015-2495C>T		intron	N/A	ENSP00000452066.2	A0A0A0MTQ3

Frequencies

GnomAD3 genomes AF: 0.0921 AC: 14007 AN: 152106 Hom.: 805 Cov.: 32

Gnomad AFR AF: 0.0361

Gnomad AMI AF: 0.166

Gnomad AMR AF: 0.0851

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.0488

Gnomad SAS AF: 0.0783

Gnomad FIN AF: 0.0528

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.0920 AC: 14009 AN: 152224 Hom.: 804 Cov.: 32 AF XY: 0.0878 AC XY: 6531 AN XY: 74424

African (AFR) AF: 0.0361 AC: 1500 AN: 41556

American (AMR) AF: 0.0849 AC: 1298 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 492 AN: 3472

East Asian (EAS) AF: 0.0488 AC: 253 AN: 5188

South Asian (SAS) AF: 0.0780 AC: 376 AN: 4822

European-Finnish (FIN) AF: 0.0528 AC: 559 AN: 10594

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9112 AN: 67984

Other (OTH) AF: 0.104 AC: 220 AN: 2114

Alfa AF: 0.120 Hom.: 672

Bravo AF: 0.0915

Asia WGS AF: 0.0750 AC: 262 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	9.1
DANN	Benign	0.81
PhyloP100		0.32
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: rs17375557; hg19: chr12-96918529;