chr12-121957871-A-G

Position:

• chr12-121957871-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.1731-401A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.858 in 152,106 control chromosomes in the GnomAD database, including 56,071 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 0.86 (56071 hom., cov: 31)
• Consequence: CFAP251 NM_144668.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP251	NM_144668.6	c.1731-401A>G		intron_variant		ENST00000288912.9	NP_653269.3
CFAP251	NM_001178003.2	c.1731-401A>G		intron_variant			NP_001171474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP251	ENST00000288912.9	c.1731-401A>G		intron_variant		1	NM_144668.6	ENSP00000288912
CFAP251	ENST00000397454.2	c.1731-401A>G		intron_variant		1		ENSP00000380595	P1
CFAP251	ENST00000535257.1	n.1836-401A>G		intron_variant, non_coding_transcript_variant		3
CFAP251	ENST00000543211.5	n.4278-401A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.858 AC: 130443 AN: 151988 Hom.: 56036 Cov.: 31

Gnomad AFR AF: 0.880

Gnomad AMI AF: 0.927

Gnomad AMR AF: 0.787

Gnomad ASJ AF: 0.900

Gnomad EAS AF: 0.817

Gnomad SAS AF: 0.854

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.873

Gnomad NFE AF: 0.869

Gnomad OTH AF: 0.854

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

GnomAD4 genome AF: 0.858 AC: 130527 AN: 152106 Hom.: 56071 Cov.: 31 AF XY: 0.855 AC XY: 63602 AN XY: 74350

Gnomad4 AFR AF: 0.880

Gnomad4 AMR AF: 0.787

Gnomad4 ASJ AF: 0.900

Gnomad4 EAS AF: 0.816

Gnomad4 SAS AF: 0.854

Gnomad4 FIN AF: 0.808

Gnomad4 NFE AF: 0.869

Gnomad4 OTH AF: 0.856

Alfa AF: 0.865 Hom.: 69626

Bravo AF: 0.857

Asia WGS AF: 0.830 AC: 2884 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.88
DANN	Benign	0.75

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: rs830124; hg19: chr12-122395777;