1-43181750-A-G

Position:

chr1-43181750-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001378189.1(CFAP57):c.374A>G(p.Gln125Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00205 in 1,614,094 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00093 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 4 hom. )

Consequence

CFAP57
NM_001378189.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 5.28

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:

LOC105378685 (HGNC:):

LOC105378685 links:

EBNA1BP2 (HGNC:15531): (EBNA1 binding protein 2) Enables RNA binding activity. Predicted to be involved in rRNA processing and ribosomal large subunit biogenesis. Located in chromosome and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

EBNA1BP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.030551821).

BP6

Variant 1-43181750-A-G is Benign according to our data. Variant chr1-43181750-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3024901.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 142 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP57	NM_001378189.1 linkuse as main transcript	c.374A>G	p.Gln125Arg	missense_variant	3/23	ENST00000372492.9	NP_001365118.1
LOC105378685	XR_007066041.1 linkuse as main transcript	n.704T>C		non_coding_transcript_exon_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP57	ENST00000372492.9 linkuse as main transcript	c.374A>G	p.Gln125Arg	missense_variant	3/23	5	NM_001378189.1	ENSP00000361570	P1	Q96MR6-1

Frequencies

GnomAD3 genomes

AF:

0.000933

AC:

142

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00176

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00101

AC:

255

AN:

251410

Hom.:

AF XY:

0.000994

AC XY:

135

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000434

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.00202

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.00217

AC:

3167

AN:

1461862

Hom.:

Cov.:

AF XY:

0.00210

AC XY:

1527

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000335

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000225

Gnomad4 NFE exome

AF:

0.00269

Gnomad4 OTH exome

AF:

0.00240

GnomAD4 genome

AF:

0.000933

AC:

142

AN:

152232

Hom.:

Cov.:

AF XY:

0.000807

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.000314

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00176

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.00188

Hom.:

Bravo

AF:

0.00111

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00244

AC:

ExAC

AF:

0.00101

AC:

122

EpiCase

AF:

0.00169

EpiControl

AF:

0.00130

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

CFAP57-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 08, 2024

This 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). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2024

CFAP57: BP4, BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

0.0

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.071

T;.;T;T

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.79

T;T;T;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.031

T;T;T;T

MetaSVM

Benign

-0.61

MutationTaster

Benign

0.97

D;D

PrimateAI

Benign

0.45

PROVEAN

Uncertain

-2.7

D;D;.;D

REVEL

Benign

0.25

Sift

Uncertain

0.025

D;D;.;D

Sift4G

Uncertain

0.013

D;D;D;D

Polyphen

0.69

P;D;.;.

Vest4

0.66

MVP

0.47

MPC

0.54

ClinPred

0.082

GERP RS

5.6

Varity_R

0.37

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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