12-96557356-A-C

Position:

• chr12-96557356-A-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP54	NM_001306084.2	c.2410+2554A>C		intron_variant		ENST00000524981.9
CFAP54	NM_001367885.1	c.2410+2554A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP54	ENST00000524981.9	c.2410+2554A>C		intron_variant		5	NM_001306084.2	P1
CFAP54	ENST00000554108.6	n.593+2554A>C		intron_variant, non_coding_transcript_variant		5
CFAP54	ENST00000556591.1	n.251+2554A>C		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.0727

Gnomad4 ASJ AF: 0.0256

Gnomad4 EAS AF: 0.0568

Gnomad4 SAS AF: 0.00994

Gnomad4 FIN AF: 0.0152

Gnomad4 NFE AF: 0.00901

Gnomad4 OTH AF: 0.0629

Alfa AF: 0.0117 Hom.: 8

Bravo AF: 0.0755

Asia WGS AF: 0.0600 AC: 208 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.6
DANN	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs725214; hg19: chr12-96951134;