rs1802074

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003014.4(SFRP4):c.1019G>A(p.Arg340Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 1,611,698 control chromosomes in the GnomAD database, including 36,456 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4872 hom., cov: 32)

Exomes 𝑓: 0.20 ( 31584 hom. )

Consequence

SFRP4
NM_003014.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.695

Publications

45 publications found

Variant links:

Genes affected

SFRP4 (HGNC:10778): (secreted frizzled related protein 4) Secreted frizzled-related protein 4 (SFRP4) is 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. The expression of SFRP4 in ventricular myocardium correlates with apoptosis related gene expression. [provided by RefSeq, Jul 2008]

SFRP4 Gene-Disease associations (from GenCC):

Pyle disease
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

SFRP4 links:

ENSG00000290149 (HGNC:):

ENSG00000290149 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003261745).

BP6

Variant 7-37907501-C-T is Benign according to our data. Variant chr7-37907501-C-T is described in ClinVar as Benign. ClinVar VariationId is 1332946.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFRP4	NM_003014.4 link	c.1019G>A	p.Arg340Lys	missense_variant	Exon 6 of 6	ENST00000436072.7	NP_003005.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
SFRP4	ENST00000436072.7 link	c.1019G>A	p.Arg340Lys	missense_variant	Exon 6 of 6	1	NM_003014.4	ENSP00000410715.2
ENSG00000290149	ENST00000476620.1 link	c.-37-41339C>T		intron_variant	Intron 2 of 3	4		ENSP00000425858.1
SFRP4	ENST00000478975.1 link	n.387G>A		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.242

AC:

36804

AN:

151968

Hom.:

4866

Cov.:

show subpopulations

Gnomad AFR

AF:

0.348

Gnomad AMI

AF:

0.170

Gnomad AMR

AF:

0.161

Gnomad ASJ

AF:

0.206

Gnomad EAS

AF:

0.245

Gnomad SAS

AF:

0.130

Gnomad FIN

AF:

0.259

Gnomad MID

AF:

0.304

Gnomad NFE

AF:

0.204

Gnomad OTH

AF:

0.233

GnomAD2 exomes

AF:

0.198

AC:

49610

AN:

250532

AF XY:

0.196

show subpopulations

Gnomad AFR exome

AF:

0.353

Gnomad AMR exome

AF:

0.0997

Gnomad ASJ exome

AF:

0.216

Gnomad EAS exome

AF:

0.246

Gnomad FIN exome

AF:

0.246

Gnomad NFE exome

AF:

0.205

Gnomad OTH exome

AF:

0.199

GnomAD4 exome

AF:

0.204

AC:

298058

AN:

1459612

Hom.:

31584

Cov.:

AF XY:

0.203

AC XY:

147216

AN XY:

726192

show subpopulations

African (AFR)

AF:

0.346

AC:

11513

AN:

33292

American (AMR)

AF:

0.105

AC:

4653

AN:

44504

Ashkenazi Jewish (ASJ)

AF:

0.218

AC:

5689

AN:

26072

East Asian (EAS)

AF:

0.240

AC:

9520

AN:

39676

South Asian (SAS)

AF:

0.135

AC:

11583

AN:

86066

European-Finnish (FIN)

AF:

0.244

AC:

13048

AN:

53388

Middle Eastern (MID)

AF:

0.271

AC:

1555

AN:

5730

European-Non Finnish (NFE)

AF:

0.205

AC:

228100

AN:

1110570

Other (OTH)

AF:

0.206

AC:

12397

AN:

60314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

11265

22531

33796

45062

56327

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7956

15912

23868

31824

39780

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.242

AC:

36839

AN:

152086

Hom.:

4872

Cov.:

AF XY:

0.241

AC XY:

17894

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.347

AC:

14396

AN:

41462

American (AMR)

AF:

0.161

AC:

2459

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.206

AC:

715

AN:

3472

East Asian (EAS)

AF:

0.246

AC:

1271

AN:

5166

South Asian (SAS)

AF:

0.130

AC:

628

AN:

4822

European-Finnish (FIN)

AF:

0.259

AC:

2743

AN:

10584

Middle Eastern (MID)

AF:

0.310

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.204

AC:

13884

AN:

67986

Other (OTH)

AF:

0.236

AC:

497

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1408

2817

4225

5634

7042

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

370

740

1110

1480

1850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.214

Hom.:

14811

Bravo

AF:

0.240

TwinsUK

AF:

0.212

AC:

786

ALSPAC

AF:

0.210

AC:

810

ESP6500AA

AF:

0.341

AC:

1503

ESP6500EA

AF:

0.192

AC:

1651

ExAC

AF:

0.203

AC:

24597

Asia WGS

AF:

0.175

AC:

608

AN:

3478

EpiCase

AF:

0.211

EpiControl

AF:

0.210

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Pyle metaphyseal dysplasia

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

SFRP4-related disorder

Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.70

CADD

Benign

4.3

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.15

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.064

LIST_S2

Benign

0.46

MetaRNN

Benign

0.0033

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

PhyloP100

0.69

PrimateAI

Benign

0.25

PROVEAN

Benign

0.020

REVEL

Benign

0.086

Sift

Benign

0.86

Sift4G

Benign

0.52

Polyphen

0.0

Vest4

0.010

MPC

0.38

ClinPred

0.000014

GERP RS

0.88

Varity_R

0.031

gMVP

0.13

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over