Genetic Variant NM_032545.4:c.260_267delGGCCGCGC (chr2-130597962-AGCGCGGCC-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_032545.4(CFC1):c.260_267delGGCCGCGC(p.Arg87LeufsTer28) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 1)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CFC1
NM_032545.4 frameshift

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.54

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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFC1	NM_032545.4 link	c.260_267delGGCCGCGC	p.Arg87LeufsTer28	frameshift_variant	Exon 4 of 6	ENST00000259216.6	NP_115934.1	P0CG37
CFC1	NM_001270420.2 link	c.248-367_248-360delGGCCGCGC		intron_variant	Intron 3 of 4		NP_001257349.1	P0CG37A0A087WWV2
CFC1	NM_001270421.2 link	c.247+672_247+679delGGCCGCGC		intron_variant	Intron 3 of 3		NP_001257350.1	P0CG37A0A087WX98
CFC1	XM_011511486.4 link	c.246_253delGGCCGCGC		downstream_gene_variant			XP_011509788.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CFC1	ENST00000259216.6 link	c.260_267delGGCCGCGC	p.Arg87LeufsTer28	frameshift_variant	Exon 4 of 6	1	NM_032545.4	ENSP00000259216.5	P0CG37
CFC1	ENST00000615342.4 link	c.248-367_248-360delGGCCGCGC		intron_variant	Intron 3 of 4	5		ENSP00000480526.1	A0A087WWV2
CFC1	ENST00000621673.4 link	c.247+672_247+679delGGCCGCGC		intron_variant	Intron 3 of 3	2		ENSP00000480843.1	A0A087WX98

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

2158

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

9898

Hom.:

AF XY:

0.00

AC XY:

AN XY:

4748

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

2156

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

958

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Jul 13, 2022

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed at significant frequency in large population cohorts (gnomAD); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene or region of a gene for which loss of function is not a well-established mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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