NM_001306084.2:c.2410+2554A>C

Variant names:

• chr12-96557356-A-C
• rs725214
• NM_001306084.2:c.2410+2554A>C

Variant summary

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

The NM_001306084.2(CFAP54):​c.2410+2554A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0633 in 152,248 control chromosomes in the GnomAD database, including 758 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 0.063 (758 hom., cov: 32)
• Consequence: CFAP54 NM_001306084.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.558
• Publications: 1 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.169 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.2410+2554A>C		intron	N/A	NP_001293013.1	Q96N23-1
	CFAP54	NM_001367885.1		c.2410+2554A>C		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.2410+2554A>C		intron	N/A	ENSP00000431759.5	Q96N23-1
	CFAP54	ENST00000554108.6	TSL:5	n.593+2554A>C		intron	N/A
	CFAP54	ENST00000556591.1	TSL:5	n.251+2554A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0631 AC: 9597 AN: 152130 Hom.: 747 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0719

Gnomad ASJ AF: 0.0256

Gnomad EAS AF: 0.0569

Gnomad SAS AF: 0.00993

Gnomad FIN AF: 0.0152

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.00901

Gnomad OTH AF: 0.0626

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

GnomAD4 genome AF: 0.0633 AC: 9638 AN: 152248 Hom.: 758 Cov.: 32 AF XY: 0.0617 AC XY: 4594 AN XY: 74448

African (AFR) AF: 0.173 AC: 7176 AN: 41518

American (AMR) AF: 0.0727 AC: 1111 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0256 AC: 89 AN: 3470

East Asian (EAS) AF: 0.0568 AC: 295 AN: 5190

South Asian (SAS) AF: 0.00994 AC: 48 AN: 4828

European-Finnish (FIN) AF: 0.0152 AC: 161 AN: 10618

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.00901 AC: 613 AN: 68020

Other (OTH) AF: 0.0629 AC: 133 AN: 2114

Alfa AF: 0.0191 Hom.: 20

Bravo AF: 0.0755

Asia WGS AF: 0.0600 AC: 208 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.6
DANN	Benign	0.57
PhyloP100		0.56
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: rs725214; hg19: chr12-96951134;