Variant chr2-130593026-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_032545.4(CFC1):c.523G>A(p.Ala175Thr) 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 0.0013 ( 0 hom., cov: 14)

Exomes 𝑓: 0.0019 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CFC1
NM_032545.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.51

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=0.0071367323).

BP6

Variant 2-130593026-C-T is Benign according to our data. Variant chr2-130593026-C-T is described in ClinVar as [Benign]. Clinvar id is 3388902.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFC1	NM_032545.4 linkuse as main transcript	c.523G>A	p.Ala175Thr	missense_variant	6/6	ENST00000259216.6	NP_115934.1	P0CG37
CFC1	NM_001270421.2 linkuse as main transcript	c.298G>A	p.Ala100Thr	missense_variant	4/4		NP_001257350.1	P0CG37A0A087WX98
CFC1	NM_001270420.2 linkuse as main transcript	c.408G>A	p.Ala136Ala	synonymous_variant	5/5		NP_001257349.1	P0CG37A0A087WWV2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CFC1	ENST00000259216.6 linkuse as main transcript	c.523G>A	p.Ala175Thr	missense_variant	6/6	1	NM_032545.4	ENSP00000259216.5	P0CG37
CFC1	ENST00000621673.4 linkuse as main transcript	c.298G>A	p.Ala100Thr	missense_variant	4/4	2		ENSP00000480843.1	A0A087WX98
CFC1	ENST00000615342.4 linkuse as main transcript	c.408G>A	p.Ala136Ala	synonymous_variant	5/5	5		ENSP00000480526.1	A0A087WWV2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

137

AN:

106250

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000776

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.000688

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00839

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00119

Gnomad OTH

AF:

0.00307

GnomAD3 exomes

AF:

0.00119

AC:

AN:

53658

Hom.:

AF XY:

0.00144

AC XY:

AN XY:

27084

show subpopulations

Gnomad AFR exome

AF:

0.000192

Gnomad AMR exome

AF:

0.00176

Gnomad ASJ exome

AF:

0.000688

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000166

Gnomad FIN exome

AF:

0.0100

Gnomad NFE exome

AF:

0.00167

Gnomad OTH exome

AF:

0.00105

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00193

AC:

857

AN:

443434

Hom.:

Cov.:

AF XY:

0.00189

AC XY:

441

AN XY:

233390

show subpopulations

Gnomad4 AFR exome

AF:

0.000247

Gnomad4 AMR exome

AF:

0.00200

Gnomad4 ASJ exome

AF:

0.000441

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000246

Gnomad4 FIN exome

AF:

0.00910

Gnomad4 NFE exome

AF:

0.00185

Gnomad4 OTH exome

AF:

0.00171

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00129

AC:

137

AN:

106316

Hom.:

Cov.:

AF XY:

0.00154

AC XY:

AN XY:

48836

show subpopulations

Gnomad4 AFR

AF:

0.0000773

Gnomad4 AMR

AF:

0.00164

Gnomad4 ASJ

AF:

0.000688

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00839

Gnomad4 NFE

AF:

0.00119

Gnomad4 OTH

AF:

0.00304

Alfa

AF:

0.000727

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2024

CFC1: PP2, BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

7.1

DANN

Uncertain

0.98

DEOGEN2

Benign

0.095

.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.00055

LIST_S2

Benign

0.50

T;T

M_CAP

Benign

0.028

MetaRNN

Benign

0.0071

T;T

MetaSVM

Benign

-0.55

PrimateAI

Benign

0.48

PROVEAN

Benign

0.55

.;N

REVEL

Benign

0.17

Sift

Benign

0.60

.;T

Sift4G

Benign

0.30

T;T

Polyphen

0.010

.;B

Vest4

0.13

MVP

0.068

MPC

2.3

ClinPred

0.026

GERP RS

-2.7

Varity_R

0.023

gMVP

0.15

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