rs587780885

Variant names:

• chr2-130592961-G-A
• rs587780885
• NM_032545.4:c.588C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-130592961-G-A
• chr2-130592961-G-C
• chr2-130592961-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM1 BP4_Moderate

The NM_001270420.2(CFC1):​c.473C>T​(p.Pro158Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 8/10 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P158Q) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 8)
  • Exomes 𝑓: 0.0000023 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CFC1 NM_001270420.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.16

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM1: In a lipid_moiety_binding_region GPI-anchor amidated aspartate (size 0) in uniprot entity CFC1_HUMAN
• BP4: Computational evidence support a benign effect (MetaRNN=0.07616305).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFC1	NM_032545.4	c.588C>T	p.Pro196Pro	synonymous_variant	Exon 6 of 6	ENST00000259216.6	NP_115934.1
CFC1	NM_001270420.2	c.473C>T	p.Pro158Leu	missense_variant	Exon 5 of 5		NP_001257349.1
CFC1	NM_001270421.2	c.363C>T	p.Pro121Pro	synonymous_variant	Exon 4 of 4		NP_001257350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFC1	ENST00000259216.6	c.588C>T	p.Pro196Pro	synonymous_variant	Exon 6 of 6	1	NM_032545.4	ENSP00000259216.5
CFC1	ENST00000615342.4	c.473C>T	p.Pro158Leu	missense_variant	Exon 5 of 5	5		ENSP00000480526.1
CFC1	ENST00000621673.4	c.363C>T	p.Pro121Pro	synonymous_variant	Exon 4 of 4	2		ENSP00000480843.1

Frequencies

GnomAD3 genomes Cov.: 8

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000229 AC: 1 AN: 437282 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 228892

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000547

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 Cov.: 8

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	9.4
DANN	Benign	0.79
FATHMM_MKL	Benign	0.00042	N
LIST_S2	Benign	0.38	T
MetaRNN	Benign	0.076	T
Vest4		0.088
MVP		0.043
GERP RS		-3.1

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

Other links and lift over

dbSNP: rs587780885; hg19: chr2-131350534;