NM_003013.3:c.78C>T

Variant names:

• chr4-153788758-G-A
• rs4076441
• NM_003013.3:c.78C>T
• SFRP2 p.Phe26Phe

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003013.3(SFRP2):​c.78C>T​(p.Phe26Phe) 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
• Publications: 4 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: Benign. The variant received -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.

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.78C>T	p.Phe26Phe	synonymous	Exon 1 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.78C>T	p.Phe26Phe	synonymous	Exon 1 of 3	ENSP00000274063.4	Q96HF1
	SFRP2	ENST00000918154.1		c.78C>T	p.Phe26Phe	synonymous	Exon 1 of 3	ENSP00000588213.1
	ENSG00000280241	ENST00000839747.1		n.99+29192G>A		intron	N/A

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

GnomAD2 exomes AF: 0.0170 AC: 4161 AN: 245324 AF XY: 0.0155

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 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

African (AFR) AF: 0.107 AC: 3568 AN: 33474

American (AMR) AF: 0.0220 AC: 986 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0408 AC: 1067 AN: 26130

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.00808 AC: 697 AN: 86252

European-Finnish (FIN) AF: 0.00124 AC: 64 AN: 51538

Middle Eastern (MID) AF: 0.0695 AC: 397 AN: 5714

European-Non Finnish (NFE) AF: 0.00677 AC: 7525 AN: 1111958

Other (OTH) AF: 0.0206 AC: 1242 AN: 60364

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

African (AFR) AF: 0.104 AC: 4304 AN: 41550

American (AMR) AF: 0.0295 AC: 451 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0384 AC: 133 AN: 3468

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5166

South Asian (SAS) AF: 0.00745 AC: 36 AN: 4832

European-Finnish (FIN) AF: 0.00104 AC: 11 AN: 10622

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.00825 AC: 561 AN: 68034

Other (OTH) AF: 0.0515 AC: 109 AN: 2116

Alfa AF: 0.0203 Hom.: 56

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	9.2
DANN	Benign	0.72
PhyloP100		1.2
PromoterAI		-0.043	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4076441;

hg19: chr4-154709910;

COSMIC: COSV56838248;