12-121921266-T-C

Position:

• chr12-121921266-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_144668.6(CFAP251):​c.-20-20T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 1,530,240 control chromosomes in the GnomAD database, including 249,641 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (26522 hom., cov: 31)
  • Exomes 𝑓: 0.56 (223119 hom.)
• Consequence: CFAP251 NM_144668.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.565

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 12-121921266-T-C is Benign according to our data. Variant chr12-121921266-T-C is described in ClinVar as [Benign]. Clinvar id is 1678711.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP251	NM_144668.6	c.-20-20T>C		intron_variant		ENST00000288912.9	NP_653269.3
CFAP251	NM_001178003.2	c.-20-20T>C		intron_variant			NP_001171474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP251	ENST00000288912.9	c.-20-20T>C		intron_variant		1	NM_144668.6	ENSP00000288912
CFAP251	ENST00000397454.2	c.-20-20T>C		intron_variant		1		ENSP00000380595	P1

Frequencies

GnomAD3 genomes AF: 0.581 AC: 88207 AN: 151778 Hom.: 26494 Cov.: 31

Gnomad AFR AF: 0.715

Gnomad AMI AF: 0.539

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.568

GnomAD3 exomes AF: 0.513 AC: 90298 AN: 176028 Hom.: 24363 AF XY: 0.517 AC XY: 48729 AN XY: 94198

Gnomad AFR exome AF: 0.718

Gnomad AMR exome AF: 0.322

Gnomad ASJ exome AF: 0.585

Gnomad EAS exome AF: 0.346

Gnomad SAS exome AF: 0.523

Gnomad FIN exome AF: 0.442

Gnomad NFE exome AF: 0.564

Gnomad OTH exome AF: 0.512

GnomAD4 exome AF: 0.565 AC: 778165 AN: 1378344 Hom.: 223119 Cov.: 44 AF XY: 0.565 AC XY: 383091 AN XY: 678470

Gnomad4 AFR exome AF: 0.726

Gnomad4 AMR exome AF: 0.341

Gnomad4 ASJ exome AF: 0.593

Gnomad4 EAS exome AF: 0.372

Gnomad4 SAS exome AF: 0.529

Gnomad4 FIN exome AF: 0.450

Gnomad4 NFE exome AF: 0.580

Gnomad4 OTH exome AF: 0.558

GnomAD4 genome AF: 0.581 AC: 88273 AN: 151896 Hom.: 26522 Cov.: 31 AF XY: 0.572 AC XY: 42480 AN XY: 74232

Gnomad4 AFR AF: 0.715

Gnomad4 AMR AF: 0.448

Gnomad4 ASJ AF: 0.609

Gnomad4 EAS AF: 0.350

Gnomad4 SAS AF: 0.521

Gnomad4 FIN AF: 0.443

Gnomad4 NFE AF: 0.572

Gnomad4 OTH AF: 0.567

Alfa AF: 0.570 Hom.: 40826

Bravo AF: 0.585

Asia WGS AF: 0.450 AC: 1566 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 22, 2022	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.8
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs6486782; hg19: chr12-122359172;