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12-121923696-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_144668.6(CFAP251):c.453C>T(p.Asp151=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000538 in 1,614,106 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00034 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00056 ( 0 hom. )

Consequence

CFAP251
NM_144668.6 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.837
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 12-121923696-C-T is Benign according to our data. Variant chr12-121923696-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3049348.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.837 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CFAP251NM_144668.6 linkuse as main transcriptc.453C>T p.Asp151= synonymous_variant 3/22 ENST00000288912.9
CFAP251NM_001178003.2 linkuse as main transcriptc.453C>T p.Asp151= synonymous_variant 3/18

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CFAP251ENST00000288912.9 linkuse as main transcriptc.453C>T p.Asp151= synonymous_variant 3/221 NM_144668.6 Q8TBY9-1
CFAP251ENST00000397454.2 linkuse as main transcriptc.453C>T p.Asp151= synonymous_variant 3/181 P1Q8TBY9-2
CFAP251ENST00000540779.1 linkuse as main transcriptn.351C>T non_coding_transcript_exon_variant 2/32

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000342
AC:
52
AN:
152100
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000656
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000676
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000284
AC:
71
AN:
249566
Hom.:
0
AF XY:
0.000288
AC XY:
39
AN XY:
135402
show subpopulations
Gnomad AFR exome
AF:
0.000323
Gnomad AMR exome
AF:
0.0000579
Gnomad ASJ exome
AF:
0.000199
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000538
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.000558
AC:
816
AN:
1461888
Hom.:
0
Cov.:
31
AF XY:
0.000567
AC XY:
412
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.000388
Gnomad4 AMR exome
AF:
0.000157
Gnomad4 ASJ exome
AF:
0.000115
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000696
Gnomad4 OTH exome
AF:
0.000298
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000342
AC:
52
AN:
152218
Hom.:
1
Cov.:
32
AF XY:
0.000161
AC XY:
12
AN XY:
74422
show subpopulations
Gnomad4 AFR
AF:
0.000120
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000676
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000654
Hom.:
0
Bravo
AF:
0.000385
EpiCase
AF:
0.000927
EpiControl
AF:
0.00101

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

CFAP251-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesJul 10, 2019This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
Cadd
Benign
0.53
Dann
Benign
0.25

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs189409230; hg19: chr12-122361602; API