NM_144668.6:c.196_197insAGAAAGAGGAGGAGG

Variant names:

• chr12-121921491-G-GGAGGAGGAGGAGAAA
• rs71082910
• NM_144668.6:c.196_197insAGAAAGAGGAGGAGG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_144668.6(CFAP251):​c.196_197insAGAAAGAGGAGGAGG​(p.Glu65_Gly66insGluLysGluGluGlu) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.88 (58980 hom., cov: 0)
  • Exomes 𝑓: 0.87 (548518 hom.)
  • Failed GnomAD Quality Control
• Consequence: CFAP251 NM_144668.6 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.809

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]

ENSG00000256950 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP251	NM_144668.6	c.196_197insAGAAAGAGGAGGAGG	p.Glu65_Gly66insGluLysGluGluGlu	disruptive_inframe_insertion	Exon 2 of 22	ENST00000288912.9	NP_653269.3
CFAP251	NM_001178003.2	c.196_197insAGAAAGAGGAGGAGG	p.Glu65_Gly66insGluLysGluGluGlu	disruptive_inframe_insertion	Exon 2 of 18		NP_001171474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP251	ENST00000288912.9	c.196_197insAGAAAGAGGAGGAGG	p.Glu65_Gly66insGluLysGluGluGlu	disruptive_inframe_insertion	Exon 2 of 22	1	NM_144668.6	ENSP00000288912.4
ENSG00000256950	ENST00000546333.1	n.*291_*292insGAGGAGGAGGAGAAA		downstream_gene_variant		5		ENSP00000477146.1

Frequencies

GnomAD3 genomes AF: 0.882 AC: 133199 AN: 151046 Hom.: 58931 Cov.: 0

Gnomad AFR AF: 0.956

Gnomad AMI AF: 0.926

Gnomad AMR AF: 0.798

Gnomad ASJ AF: 0.904

Gnomad EAS AF: 0.853

Gnomad SAS AF: 0.852

Gnomad FIN AF: 0.808

Gnomad MID AF: 0.917

Gnomad NFE AF: 0.869

Gnomad OTH AF: 0.877

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.867 AC: 1262299 AN: 1456000 Hom.: 548518 Cov.: 63 AF XY: 0.867 AC XY: 627767 AN XY: 724020

Gnomad4 AFR exome AF: 0.962

Gnomad4 AMR exome AF: 0.733

Gnomad4 ASJ exome AF: 0.898

Gnomad4 EAS exome AF: 0.852

Gnomad4 SAS exome AF: 0.851

Gnomad4 FIN exome AF: 0.815

Gnomad4 NFE exome AF: 0.872

Gnomad4 OTH exome AF: 0.874

GnomAD4 genome AF: 0.882 AC: 133303 AN: 151162 Hom.: 58980 Cov.: 0 AF XY: 0.878 AC XY: 64736 AN XY: 73750

Gnomad4 AFR AF: 0.956

Gnomad4 AMR AF: 0.798

Gnomad4 ASJ AF: 0.904

Gnomad4 EAS AF: 0.852

Gnomad4 SAS AF: 0.852

Gnomad4 FIN AF: 0.808

Gnomad4 NFE AF: 0.869

Gnomad4 OTH AF: 0.879

Alfa AF: 0.851 Hom.: 5066

Asia WGS AF: 0.842 AC: 2925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs71082910; hg19: chr12-122359397;