rs1177589

chr12-121966027-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_144668.6(CFAP251):c.2493-928A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 151,506 control chromosomes in the GnomAD database, including 35,779 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 0.65 (35779 hom., cov: 27)
• Consequence: CFAP251 NM_144668.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.473

Genes affected

CFAP251 (HGNC:28506): (cilia and flagella associated protein 251) This protein encoded by this gene belongs to the WD repeat-containing family of proteins, which function in the formation of protein-protein complexes in a variety of biological pathways. This family member appears to function in the determination of mean platelet volume (MPV), and polymorphisms in this gene have been associated with variance in MPV. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CFAP251	NM_144668.6	c.2493-928A>G		intron_variant		ENST00000288912.9
CFAP251	NM_001178003.2	c.2493-928A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CFAP251	ENST00000288912.9	c.2493-928A>G		intron_variant		1	NM_144668.6
CFAP251	ENST00000397454.2	c.2493-928A>G		intron_variant		1		P1
CFAP251	ENST00000545752.1	n.170-928A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99194 AN: 151388 Hom.: 35773 Cov.: 27

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.889

Gnomad AMR AF: 0.682

Gnomad ASJ AF: 0.853

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.778

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.822

Gnomad OTH AF: 0.698

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

GnomAD4 genome AF: 0.655 AC: 99226 AN: 151506 Hom.: 35779 Cov.: 27 AF XY: 0.652 AC XY: 48266 AN XY: 74050

Gnomad4 AFR AF: 0.338

Gnomad4 AMR AF: 0.682

Gnomad4 ASJ AF: 0.853

Gnomad4 EAS AF: 0.532

Gnomad4 SAS AF: 0.573

Gnomad4 FIN AF: 0.778

Gnomad4 NFE AF: 0.822

Gnomad4 OTH AF: 0.701

Alfa AF: 0.718 Hom.: 5182

Bravo AF: 0.638

Asia WGS AF: 0.548 AC: 1907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	5.3
Dann	Benign	0.66

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: rs1177589; hg19: chr12-122403933;