12-122001463-T-C

Position:

• chr12-122001463-T-C

Variant summary

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

The ENST00000288912.9(CFAP251):​c.3236-34T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.868 in 1,550,826 control chromosomes in the GnomAD database, including 586,059 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 0.88 (58812 hom., cov: 31)
  • Exomes 𝑓: 0.87 (527247 hom.)
• Consequence: CFAP251 ENST00000288912.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900

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]

LOC124903038 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP251	NM_144668.6	c.3236-34T>C		intron_variant		ENST00000288912.9	NP_653269.3
LOC124903038	XR_007063499.1	n.89+4149A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP251	ENST00000288912.9	c.3236-34T>C		intron_variant		1	NM_144668.6	ENSP00000288912
CFAP251	ENST00000428465.2	n.3060-34T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.878 AC: 133475 AN: 152002 Hom.: 58765 Cov.: 31

Gnomad AFR AF: 0.944

Gnomad AMI AF: 0.953

Gnomad AMR AF: 0.795

Gnomad ASJ AF: 0.895

Gnomad EAS AF: 0.855

Gnomad SAS AF: 0.858

Gnomad FIN AF: 0.807

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.869

Gnomad OTH AF: 0.868

GnomAD3 exomes AF: 0.847 AC: 211296 AN: 249502 Hom.: 90001 AF XY: 0.851 AC XY: 115226 AN XY: 135364

Gnomad AFR exome AF: 0.947

Gnomad AMR exome AF: 0.725

Gnomad ASJ exome AF: 0.887

Gnomad EAS exome AF: 0.853

Gnomad SAS exome AF: 0.859

Gnomad FIN exome AF: 0.813

Gnomad NFE exome AF: 0.868

Gnomad OTH exome AF: 0.856

GnomAD4 exome AF: 0.867 AC: 1213171 AN: 1398706 Hom.: 527247 Cov.: 22 AF XY: 0.868 AC XY: 607377 AN XY: 699980

Gnomad4 AFR exome AF: 0.949

Gnomad4 AMR exome AF: 0.731

Gnomad4 ASJ exome AF: 0.888

Gnomad4 EAS exome AF: 0.855

Gnomad4 SAS exome AF: 0.857

Gnomad4 FIN exome AF: 0.816

Gnomad4 NFE exome AF: 0.874

Gnomad4 OTH exome AF: 0.872

GnomAD4 genome AF: 0.878 AC: 133579 AN: 152120 Hom.: 58812 Cov.: 31 AF XY: 0.874 AC XY: 65005 AN XY: 74358

Gnomad4 AFR AF: 0.944

Gnomad4 AMR AF: 0.794

Gnomad4 ASJ AF: 0.895

Gnomad4 EAS AF: 0.855

Gnomad4 SAS AF: 0.858

Gnomad4 FIN AF: 0.807

Gnomad4 NFE AF: 0.869

Gnomad4 OTH AF: 0.870

Alfa AF: 0.853 Hom.: 16068

Bravo AF: 0.880

Asia WGS AF: 0.852 AC: 2962 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.1
DANN	Benign	0.70

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: rs1182927; hg19: chr12-122439369;