rs4076441

chr4-153788758-G-Achr4-153788758-G-Cchr4-153788758-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003013.3(SFRP2):c.78C>T(p.Phe26=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0131 in 1,612,152 control chromosomes in the GnomAD database, including 518 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.037 (240 hom., cov: 32)
  • Exomes 𝑓: 0.011 (278 hom.)
• Consequence: SFRP2 NM_003013.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP7: Synonymous conserved (PhyloP=1.21 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFRP2	NM_003013.3	c.78C>T	p.Phe26=	synonymous_variant	1/3	ENST00000274063.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFRP2	ENST00000274063.5	c.78C>T	p.Phe26=	synonymous_variant	1/3	1	NM_003013.3	P1

Frequencies

GnomAD3 genomes AF: 0.0371 AC: 5639 AN: 152186 Hom.: 240 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0296

Gnomad ASJ AF: 0.0384

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00724

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.00826

Gnomad OTH AF: 0.0530

GnomAD3 exomes AF: 0.0170 AC: 4161 AN: 245324 Hom.: 103 AF XY: 0.0155 AC XY: 2080 AN XY: 133934

Gnomad AFR exome AF: 0.109

Gnomad AMR exome AF: 0.0205

Gnomad ASJ exome AF: 0.0437

Gnomad EAS exome AF: 0.000110

Gnomad SAS exome AF: 0.00820

Gnomad FIN exome AF: 0.00116

Gnomad NFE exome AF: 0.00879

Gnomad OTH exome AF: 0.0230

GnomAD4 exome AF: 0.0107 AC: 15548 AN: 1459848 Hom.: 278 Cov.: 35 AF XY: 0.0106 AC XY: 7686 AN XY: 726274

Gnomad4 AFR exome AF: 0.107

Gnomad4 AMR exome AF: 0.0220

Gnomad4 ASJ exome AF: 0.0408

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00808

Gnomad4 FIN exome AF: 0.00124

Gnomad4 NFE exome AF: 0.00677

Gnomad4 OTH exome AF: 0.0206

GnomAD4 genome AF: 0.0370 AC: 5639 AN: 152304 Hom.: 240 Cov.: 32 AF XY: 0.0367 AC XY: 2731 AN XY: 74472

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.0295

Gnomad4 ASJ AF: 0.0384

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.00745

Gnomad4 FIN AF: 0.00104

Gnomad4 NFE AF: 0.00825

Gnomad4 OTH AF: 0.0515

Alfa AF: 0.0187 Hom.: 39

Bravo AF: 0.0428

Asia WGS AF: 0.0100 AC: 36 AN: 3478

EpiCase AF: 0.0124

EpiControl AF: 0.0132

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	9.2
Dann	Benign	0.72

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: rs4076441; hg19: chr4-154709910; COSMIC: COSV56838248;