rs763890885

Variant names:

• chr4-153781567-G-C
• rs763890885
• NM_003013.3:c.772C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_003013.3(SFRP2):​c.772C>G​(p.Leu258Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000589 in 1,614,064 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000062 (0 hom.)
• Consequence: SFRP2 NM_003013.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.75
• Publications: 1 publications found

Genes affected

SFRP2 (HGNC:10777): (secreted frizzled related protein 2) This gene encodes a member of the SFRP family that contains a cysteine-rich domain homologous to the putative Wnt-binding site of Frizzled proteins. SFRPs act as soluble modulators of Wnt signaling. Methylation of this gene is a potential marker for the presence of colorectal cancer. [provided by RefSeq, Jul 2008]

ENSG00000280241 (HGNC:58900):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 5 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003013.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFRP2	NM_003013.3	MANE Select	c.772C>G	p.Leu258Val	missense	Exon 3 of 3	NP_003004.1	A0A140VJU3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFRP2	ENST00000274063.5	TSL:1 MANE Select	c.772C>G	p.Leu258Val	missense	Exon 3 of 3	ENSP00000274063.4	Q96HF1
	SFRP2	ENST00000918154.1		c.757C>G	p.Leu253Val	missense	Exon 3 of 3	ENSP00000588213.1
	ENSG00000280241	ENST00000839747.1		n.99+22001G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152192 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI 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: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000159 AC: 4 AN: 251478 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000616 AC: 90 AN: 1461872 Hom.: 0 Cov.: 31 AF XY: 0.0000646 AC XY: 47 AN XY: 727238

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000791 AC: 88 AN: 1111992

Other (OTH) AF: 0.0000331 AC: 2 AN: 60394

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152192 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74356

African (AFR) AF: 0.00 AC: 0 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000847 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.000164

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	0.080
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-0.51	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		3.7
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.31
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.58
MVP		0.79
MPC		1.8
ClinPred		0.85	D
GERP RS		5.1
Varity_R		0.44
gMVP		0.65
Mutation Taster		=60/40	polymorphism

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

Other links and lift over

dbSNP: rs763890885; hg19: chr4-154702719; COSMIC: COSV56837662;