2-130592943-C-G

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001270420.2(CFC1):c.491G>C(p.Trp164Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 8/10 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.014 ( 4 hom., cov: 7)

Exomes 𝑓: 0.0026 ( 3 hom. )

Failed GnomAD Quality Control

Consequence

CFC1
NM_001270420.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:3

Conservation

PhyloP100: -2.04

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030456483).

BP6

Variant 2-130592943-C-G is Benign according to our data. Variant chr2-130592943-C-G is described in ClinVar as [Benign]. Clinvar id is 136738.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-130592943-C-G is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFC1	NM_032545.4 link	c.606G>C	p.Leu202Leu	synonymous_variant	Exon 6 of 6	ENST00000259216.6	NP_115934.1	P0CG37
CFC1	NM_001270420.2 link	c.491G>C	p.Trp164Ser	missense_variant	Exon 5 of 5		NP_001257349.1	P0CG37A0A087WWV2
CFC1	NM_001270421.2 link	c.381G>C	p.Leu127Leu	synonymous_variant	Exon 4 of 4		NP_001257350.1	P0CG37A0A087WX98

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CFC1	ENST00000259216.6 link	c.606G>C	p.Leu202Leu	synonymous_variant	Exon 6 of 6	1	NM_032545.4	ENSP00000259216.5	P0CG37
CFC1	ENST00000615342.4 link	c.491G>C	p.Trp164Ser	missense_variant	Exon 5 of 5	5		ENSP00000480526.1	A0A087WWV2
CFC1	ENST00000621673.4 link	c.381G>C	p.Leu127Leu	synonymous_variant	Exon 4 of 4	2		ENSP00000480843.1	A0A087WX98

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

777

AN:

57254

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0592

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0159

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:

0.000186

Gnomad OTH

AF:

0.0153

GnomAD3 exomes

AF:

0.00865

AC:

425

AN:

49118

Hom.:

AF XY:

0.00738

AC XY:

184

AN XY:

24934

show subpopulations

Gnomad AFR exome

AF:

0.0801

Gnomad AMR exome

AF:

0.00482

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000259

Gnomad OTH exome

AF:

0.00348

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00264

AC:

1148

AN:

435194

Hom.:

Cov.:

AF XY:

0.00224

AC XY:

512

AN XY:

228220

show subpopulations

Gnomad4 AFR exome

AF:

0.0755

Gnomad4 AMR exome

AF:

0.00560

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000115

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000194

Gnomad4 OTH exome

AF:

0.00584

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0136

AC:

779

AN:

57206

Hom.:

Cov.:

AF XY:

0.0149

AC XY:

352

AN XY:

23688

show subpopulations

Gnomad4 AFR

AF:

0.0592

Gnomad4 AMR

AF:

0.0159

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000186

Gnomad4 OTH

AF:

0.0153

Alfa

AF:

0.0128

Hom.:

ExAC

AF:

0.000929

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:2

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

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not specified

Benign:1

Jan 16, 2013

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-1.2

CADD

Benign

1.2

DANN

Benign

0.46

FATHMM_MKL

Benign

0.00015

LIST_S2

Benign

0.17

MetaRNN

Benign

0.0030

Vest4

0.17

MVP

0.043

GERP RS

-3.3

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