dbSNP rs863223280: CFC1:c.361_362+18dupAGGTGGGCACAGGGGTGCGC (chr2-130597849-C-CGCGCACCCCTGTGCCCACCT) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP5

The NM_032545.4(CFC1):c.361_362+18dupAGGTGGGCACAGGGGTGCGC variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 0)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CFC1
NM_032545.4 intron

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: -0.0490

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

heterotaxy, visceral, 2, autosomal
Inheritance: AD Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

CFC1 links:

ENSG00000296255 (HGNC:):

ENSG00000296255 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PP5

Variant 2-130597849-C-CGCGCACCCCTGTGCCCACCT is Pathogenic according to our data. Variant chr2-130597849-C-CGCGCACCCCTGTGCCCACCT is described in ClinVar as Pathogenic. ClinVar VariationId is 5190.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
CFC1	NM_032545.4 link	c.361_362+18dupAGGTGGGCACAGGGGTGCGC	intron_variant	Intron 4 of 5	ENST00000259216.6	NP_115934.1
CFC1	NM_001270420.2 link	c.248-266_248-247dupAGGTGGGCACAGGGGTGCGC	intron_variant	Intron 3 of 4		NP_001257349.1
CFC1	NM_001270421.2 link	c.247+773_247+792dupAGGTGGGCACAGGGGTGCGC	intron_variant	Intron 3 of 3		NP_001257350.1
CFC1	XM_011511486.4 link	c.347_366dupAGGTGGGCACAGGGGTGCGC	downstream_gene_variant			XP_011509788.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFC1	ENST00000259216.6 link	c.362+18_362+19insAGGTGGGCACAGGGGTGCGC		intron_variant	Intron 4 of 5	1	NM_032545.4	ENSP00000259216.5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

664

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

324

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

532

Other (OTH)

AF:

0.00

AC:

AN:

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Heterotaxy, visceral, 2, autosomal

Pathogenic:1

Mar 01, 2002

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.049

Mutation Taster

=39/61

disease causing (ClinVar)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over