Variant 2-130593065-A-G 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.484T>C(p.Phe162Leu) variant causes a missense 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 0.0053 ( 0 hom., cov: 19)

Exomes 𝑓: 0.00087 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

CFC1
NM_032545.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.235

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=0.008504361).

BP6

Variant 2-130593065-A-G is Benign according to our data. Variant chr2-130593065-A-G is described in ClinVar as [Benign]. Clinvar id is 801752.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CFC1	NM_032545.4 linkuse as main transcript	c.484T>C	p.Phe162Leu	missense_variant	6/6	ENST00000259216.6	NP_115934.1
CFC1	NM_001270421.2 linkuse as main transcript	c.259T>C	p.Phe87Leu	missense_variant	4/4		NP_001257350.1
CFC1	NM_001270420.2 linkuse as main transcript	c.369T>C	p.Thr123=	synonymous_variant	5/5		NP_001257349.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CFC1	ENST00000259216.6 linkuse as main transcript	c.484T>C	p.Phe162Leu	missense_variant	6/6	1	NM_032545.4	ENSP00000259216	P1
CFC1	ENST00000621673.4 linkuse as main transcript	c.259T>C	p.Phe87Leu	missense_variant	4/4	2		ENSP00000480843
CFC1	ENST00000615342.4 linkuse as main transcript	c.369T>C	p.Thr123=	synonymous_variant	5/5	5		ENSP00000480526

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

673

AN:

128156

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0200

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00285

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:

0.0000486

Gnomad OTH

AF:

0.00369

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000867

AC:

356

AN:

410748

Hom.:

Cov.:

AF XY:

0.000674

AC XY:

146

AN XY:

216528

show subpopulations

Gnomad4 AFR exome

AF:

0.0231

Gnomad4 AMR exome

AF:

0.00184

Gnomad4 ASJ exome

AF:

0.0000786

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000135

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000851

Gnomad4 OTH exome

AF:

0.00181

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00529

AC:

678

AN:

128270

Hom.:

Cov.:

AF XY:

0.00490

AC XY:

299

AN XY:

61034

show subpopulations

Gnomad4 AFR

AF:

0.0200

Gnomad4 AMR

AF:

0.00285

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000486

Gnomad4 OTH

AF:

0.00364

Alfa

AF:

0.00513

Hom.:

ExAC

AF:

0.000344

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Heterotaxy, visceral, 2, autosomal

Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.69

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Benign

DANN

Benign

0.75

DEOGEN2

Benign

0.18

.;T

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.49

T;T

MetaRNN

Benign

0.0085

T;T

MetaSVM

Benign

-0.72

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.61

.;N

REVEL

Uncertain

0.51

Sift

Benign

0.40

.;T

Sift4G

Pathogenic

0.0

D;T

Polyphen

0.0080

.;B

Vest4

0.25

MutPred

0.75

.;Gain of disorder (P = 0.0994);

MVP

0.93

MPC

1.5

ClinPred

0.0011

GERP RS

0.92

Varity_R

0.043

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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