Variant 1-43181751-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001378189.1(CFAP57):c.375G>C(p.Gln125His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000228 in 1,614,020 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 Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q125R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 1 hom. )

Consequence

CFAP57
NM_001378189.1 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.01

Variant links:

Genes affected

CFAP57 (HGNC:26485): (cilia and flagella associated protein 57) 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 is thought to function in craniofacial development, possibly in the fusion of lip and palate. A missense mutation in this gene is associated with Van der Woude syndrome 2. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2011]

CFAP57 links:

EBNA1BP2 (HGNC:):

EBNA1BP2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005279094).

BP6

Variant 1-43181751-G-C is Benign according to our data. Variant chr1-43181751-G-C is described in ClinVar as [Benign]. Clinvar id is 3040861.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 46 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP57	NM_001378189.1 linkuse as main transcript	c.375G>C	p.Gln125His	missense_variant	3/23	ENST00000372492.9	NP_001365118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP57	ENST00000372492.9 linkuse as main transcript	c.375G>C	p.Gln125His	missense_variant	3/23	5	NM_001378189.1	ENSP00000361570.4		Q96MR6-1

Frequencies

GnomAD3 genomes

AF:

0.000302

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.0115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000418

AC:

105

AN:

251388

Hom.:

AF XY:

0.000361

AC XY:

AN XY:

135866

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00893

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000967

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000220

AC:

322

AN:

1461878

Hom.:

Cov.:

AF XY:

0.000212

AC XY:

154

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00945

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000369

Gnomad4 OTH exome

AF:

0.000546

GnomAD4 genome

AF:

0.000302

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.0115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000589

Hom.:

Bravo

AF:

0.000276

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000272

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

CFAP57-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 14, 2019

This variant is classified as 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

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.089

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.076

T;.;T;T

Eigen

Benign

-0.096

Eigen_PC

Benign

-0.040

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.74

T;T;T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.0053

T;T;T;T

MetaSVM

Benign

-0.91

MutationTaster

Benign

0.89

D;D

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-3.4

D;D;.;D

REVEL

Benign

0.20

Sift

Uncertain

0.0060

D;D;.;D

Sift4G

Uncertain

0.0060

D;D;D;D

Polyphen

0.025

B;B;.;.

Vest4

0.38

MutPred

0.38

Gain of disorder (P = 0.1125);Gain of disorder (P = 0.1125);Gain of disorder (P = 0.1125);Gain of disorder (P = 0.1125);

MVP

0.24

MPC

0.20

ClinPred

0.059

GERP RS

3.7

Varity_R

0.36

gMVP

0.63

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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over