Variant chr2-130592961-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_032545.4(CFC1):c.588C>A(p.Pro196=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.034 ( 31 hom., cov: 8)

Exomes 𝑓: 0.0073 ( 27 hom. )

Failed GnomAD Quality Control

Consequence

CFC1
NM_032545.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:3

Conservation

PhyloP100: -6.16

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 -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023072362).

BP6

Variant 2-130592961-G-T is Benign according to our data. Variant chr2-130592961-G-T is described in ClinVar as [Benign]. Clinvar id is 136736.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-130592961-G-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-6.16 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CFC1	NM_032545.4 linkuse as main transcript	c.588C>A	p.Pro196=	synonymous_variant	6/6	ENST00000259216.6
CFC1	NM_001270420.2 linkuse as main transcript	c.473C>A	p.Pro158Gln	missense_variant	5/5
CFC1	NM_001270421.2 linkuse as main transcript	c.363C>A	p.Pro121=	synonymous_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CFC1	ENST00000259216.6 linkuse as main transcript	c.588C>A	p.Pro196=	synonymous_variant	6/6	1	NM_032545.4	P1
CFC1	ENST00000615342.4 linkuse as main transcript	c.473C>A	p.Pro158Gln	missense_variant	5/5	5
CFC1	ENST00000621673.4 linkuse as main transcript	c.363C>A	p.Pro121=	synonymous_variant	4/4	2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

2182

AN:

63360

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.152

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0277

Gnomad ASJ

AF:

0.00431

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0210

Gnomad NFE

AF:

0.000427

Gnomad OTH

AF:

0.0456

GnomAD3 exomes

AF:

0.0222

AC:

1106

AN:

49756

Hom.:

AF XY:

0.0188

AC XY:

474

AN XY:

25264

show subpopulations

Gnomad AFR exome

AF:

0.200

Gnomad AMR exome

AF:

0.0126

Gnomad ASJ exome

AF:

0.00504

Gnomad EAS exome

AF:

0.000135

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00103

Gnomad OTH exome

AF:

0.00852

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00729

AC:

3179

AN:

436368

Hom.:

Cov.:

AF XY:

0.00607

AC XY:

1387

AN XY:

228514

show subpopulations

Gnomad4 AFR exome

AF:

0.190

Gnomad4 AMR exome

AF:

0.0150

Gnomad4 ASJ exome

AF:

0.00465

Gnomad4 EAS exome

AF:

0.0000328

Gnomad4 SAS exome

AF:

0.000366

Gnomad4 FIN exome

AF:

0.000242

Gnomad4 NFE exome

AF:

0.000826

Gnomad4 OTH exome

AF:

0.0163

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0344

AC:

2178

AN:

63326

Hom.:

Cov.:

AF XY:

0.0365

AC XY:

968

AN XY:

26526

show subpopulations

Gnomad4 AFR

AF:

0.151

Gnomad4 AMR

AF:

0.0277

Gnomad4 ASJ

AF:

0.00431

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000427

Gnomad4 OTH

AF:

0.0452

Alfa

AF:

0.00700

Hom.:

ExAC

AF:

0.000387

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 16, 2013

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

-1.0

BayesDel_noAF

Benign

-1.1

CADD

Benign

5.0

DANN

Benign

0.67

FATHMM_MKL

Benign

0.00029

LIST_S2

Benign

0.24

MetaRNN

Benign

0.0023

MutationTaster

Benign

1.0

Vest4

0.14

GERP RS

-3.1

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