2-130597533-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBP6_Very_Strong

The NM_032545.4(CFC1):c.433G>A(p.Ala145Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 0)

Exomes 𝑓: 0.072 ( 5 hom. )

Failed GnomAD Quality Control

Consequence

CFC1
NM_032545.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.143

Variant links:

Genes affected

CFC1 (HGNC:18292): (cryptic, EGF-CFC family member 1) This gene encodes a member of the epidermal growth factor (EGF)- Cripto, Frl-1, and Cryptic (CFC) family, which are involved in signalling during embryonic development. Proteins in this family share a variant EGF-like motif, a conserved cysteine-rich domain, and a C-terminal hydrophobic region. The protein encoded by this gene is necessary for patterning the left-right embryonic axis. Mutations in this gene are associated with defects in organ development, including autosomal visceral heterotaxy and congenital heart disease. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]

CFC1 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=0.17100677).

BP6

Variant 2-130597533-C-T is Benign according to our data. Variant chr2-130597533-C-T is described in ClinVar as [Benign]. Clinvar id is 136735.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-130597533-C-T is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFC1	NM_032545.4 link	c.433G>A	p.Ala145Thr	missense_variant	Exon 5 of 6	ENST00000259216.6	NP_115934.1	P0CG37
CFC1	NM_001270420.2 link	c.318G>A	p.Gly106Gly	synonymous_variant	Exon 4 of 5		NP_001257349.1	P0CG37A0A087WWV2
CFC1	NM_001270421.2 link	c.247+1109G>A		intron_variant	Intron 3 of 3		NP_001257350.1	P0CG37A0A087WX98

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CFC1	ENST00000259216.6 link	c.433G>A	p.Ala145Thr	missense_variant	Exon 5 of 6	1	NM_032545.4	ENSP00000259216.5	P0CG37
CFC1	ENST00000615342.4 link	c.318G>A	p.Gly106Gly	synonymous_variant	Exon 4 of 5	5		ENSP00000480526.1	A0A087WWV2
CFC1	ENST00000621673.4 link	c.247+1109G>A		intron_variant	Intron 3 of 3	2		ENSP00000480843.1	A0A087WX98

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

Hom.:

Cov.:

FAILED QC

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0717

AC:

5279

AN:

73600

Hom.:

Cov.:

AF XY:

0.0688

AC XY:

2649

AN XY:

38478

show subpopulations

Gnomad4 AFR exome

AF:

0.0207

Gnomad4 AMR exome

AF:

0.0606

Gnomad4 ASJ exome

AF:

0.0973

Gnomad4 EAS exome

AF:

0.00101

Gnomad4 SAS exome

AF:

0.0357

Gnomad4 FIN exome

AF:

0.0504

Gnomad4 NFE exome

AF:

0.0887

Gnomad4 OTH exome

AF:

0.0724

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0282

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Dec 18, 2012

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Heterotaxy, visceral, 2, autosomal

Benign:1

May 28, 2019

Mendelics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.79

DEOGEN2

Benign

0.11

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0052

LIST_S2

Benign

0.20

M_CAP

Uncertain

0.29

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.95

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.18

REVEL

Benign

0.22

Sift

Benign

0.73

Sift4G

Benign

0.62

Polyphen

0.0010

Vest4

0.13

MPC

1.3

ClinPred

0.00030

GERP RS

-0.52

Varity_R

0.031

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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