chr2-130598749-C-T

Position:

chr2-130598749-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_032545.4(CFC1):c.140G>A(p.Arg47Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0098 in 1,604,432 control chromosomes in the GnomAD database, including 376 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.051 ( 182 hom., cov: 22)

Exomes 𝑓: 0.0056 ( 194 hom. )

Consequence

CFC1
NM_032545.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:3

Conservation

PhyloP100: 0.668

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0109401345).

BP6

Variant 2-130598749-C-T is Benign according to our data. Variant chr2-130598749-C-T is described in ClinVar as [Benign]. Clinvar id is 136733.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-130598749-C-T is described in Lovd as [Benign]. Variant chr2-130598749-C-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CFC1	NM_032545.4 linkuse as main transcript	c.140G>A	p.Arg47Gln	missense_variant	3/6	ENST00000259216.6
CFC1	NM_001270420.2 linkuse as main transcript	c.140G>A	p.Arg47Gln	missense_variant	3/5
CFC1	NM_001270421.2 linkuse as main transcript	c.140G>A	p.Arg47Gln	missense_variant	3/4
CFC1	XM_011511486.4 linkuse as main transcript	c.140G>A	p.Arg47Gln	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CFC1	ENST00000259216.6 linkuse as main transcript	c.140G>A	p.Arg47Gln	missense_variant	3/6	1	NM_032545.4	P1
CFC1	ENST00000615342.4 linkuse as main transcript	c.140G>A	p.Arg47Gln	missense_variant	3/5	5
CFC1	ENST00000621673.4 linkuse as main transcript	c.140G>A	p.Arg47Gln	missense_variant	3/4	2

Frequencies

GnomAD3 genomes

AF:

0.0512

AC:

7532

AN:

147250

Hom.:

183

Cov.:

show subpopulations

Gnomad AFR

AF:

0.190

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0242

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000692

Gnomad OTH

AF:

0.0385

GnomAD3 exomes

AF:

0.0136

AC:

3330

AN:

244282

Hom.:

AF XY:

0.0103

AC XY:

1367

AN XY:

133214

show subpopulations

Gnomad AFR exome

AF:

0.201

Gnomad AMR exome

AF:

0.0105

Gnomad ASJ exome

AF:

0.00110

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000631

Gnomad OTH exome

AF:

0.00784

GnomAD4 exome

AF:

0.00561

AC:

8174

AN:

1457096

Hom.:

194

Cov.:

AF XY:

0.00484

AC XY:

3510

AN XY:

725170

show subpopulations

Gnomad4 AFR exome

AF:

0.203

Gnomad4 AMR exome

AF:

0.0109

Gnomad4 ASJ exome

AF:

0.000995

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000429

Gnomad4 FIN exome

AF:

0.000150

Gnomad4 NFE exome

AF:

0.000526

Gnomad4 OTH exome

AF:

0.0138

GnomAD4 genome

AF:

0.0512

AC:

7547

AN:

147336

Hom.:

182

Cov.:

AF XY:

0.0497

AC XY:

3589

AN XY:

72142

show subpopulations

Gnomad4 AFR

AF:

0.190

Gnomad4 AMR

AF:

0.0242

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000692

Gnomad4 OTH

AF:

0.0381

Alfa

AF:

0.0270

Hom.:

ExAC

AF:

0.0192

AC:

2332

EpiCase

AF:

0.00109

EpiControl

AF:

0.000950

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 07, 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. -

not provided

Benign:1

Likely benign, no assertion criteria provided

clinical testing

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.44

CADD

Benign

6.0

DANN

Benign

0.25

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.00012

LIST_S2

Benign

0.45

T;T;T

MetaRNN

Benign

0.011

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.35

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

.;.;B

Vest4

0.16

MPC

1.5

ClinPred

0.0013

GERP RS

0.60

Varity_R

0.024

gMVP

0.062

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