chr7-37907562-G-T

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.958C>A(p.Pro320Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.405 in 1,612,272 control chromosomes in the GnomAD database, including 135,524 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 0.46 ( 16582 hom., cov: 32)

Exomes 𝑓: 0.40 ( 118942 hom. )

Consequence

SFRP4
NM_003014.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.432

Publications

61 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=4.5010467E-5).

BP6

Variant 7-37907562-G-T is Benign according to our data. Variant chr7-37907562-G-T is described in CliVar as Benign. Clinvar id is 1287094.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-37907562-G-T is described in CliVar as Benign. Clinvar id is 1287094.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-37907562-G-T is described in CliVar as Benign. Clinvar id is 1287094.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-37907562-G-T is described in CliVar as Benign. Clinvar id is 1287094.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-37907562-G-T is described in CliVar as Benign. Clinvar id is 1287094.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-37907562-G-T is described in CliVar as Benign. Clinvar id is 1287094.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFRP4	NM_003014.4 link	c.958C>A	p.Pro320Thr	missense_variant	Exon 6 of 6	ENST00000436072.7	NP_003005.2	Q6FHJ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SFRP4	ENST00000436072.7 link	c.958C>A	p.Pro320Thr	missense_variant	Exon 6 of 6	1	NM_003014.4	ENSP00000410715.2	Q6FHJ7
ENSG00000290149	ENST00000476620.1 link	c.-37-41278G>T		intron_variant	Intron 2 of 3	4		ENSP00000425858.1	D6RIH7
SFRP4	ENST00000478975.1 link	n.326C>A		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.456

AC:

69168

AN:

151686

Hom.:

16558

Cov.:

show subpopulations

Gnomad AFR

AF:

0.577

Gnomad AMI

AF:

0.349

Gnomad AMR

AF:

0.490

Gnomad ASJ

AF:

0.411

Gnomad EAS

AF:

0.551

Gnomad SAS

AF:

0.526

Gnomad FIN

AF:

0.405

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.374

Gnomad OTH

AF:

0.455

GnomAD2 exomes

AF:

0.437

AC:

109702

AN:

251174

AF XY:

0.435

show subpopulations

Gnomad AFR exome

AF:

0.584

Gnomad AMR exome

AF:

0.465

Gnomad ASJ exome

AF:

0.423

Gnomad EAS exome

AF:

0.553

Gnomad FIN exome

AF:

0.394

Gnomad NFE exome

AF:

0.375

Gnomad OTH exome

AF:

0.416

GnomAD4 exome

AF:

0.400

AC:

583939

AN:

1460468

Hom.:

118942

Cov.:

AF XY:

0.403

AC XY:

292492

AN XY:

726542

show subpopulations

African (AFR)

AF:

0.579

AC:

19372

AN:

33434

American (AMR)

AF:

0.466

AC:

20849

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.424

AC:

11069

AN:

26110

East Asian (EAS)

AF:

0.524

AC:

20805

AN:

39672

South Asian (SAS)

AF:

0.522

AC:

44958

AN:

86172

European-Finnish (FIN)

AF:

0.394

AC:

21033

AN:

53396

Middle Eastern (MID)

AF:

0.474

AC:

2702

AN:

5698

European-Non Finnish (NFE)

AF:

0.376

AC:

418197

AN:

1110952

Other (OTH)

AF:

0.414

AC:

24954

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

17788

35576

53364

71152

88940

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13476

26952

40428

53904

67380

<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:

0.456

AC:

69240

AN:

151804

Hom.:

16582

Cov.:

AF XY:

0.460

AC XY:

34099

AN XY:

74178

show subpopulations

African (AFR)

AF:

0.577

AC:

23851

AN:

41344

American (AMR)

AF:

0.491

AC:

7490

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.411

AC:

1426

AN:

3472

East Asian (EAS)

AF:

0.551

AC:

2834

AN:

5144

South Asian (SAS)

AF:

0.526

AC:

2528

AN:

4806

European-Finnish (FIN)

AF:

0.405

AC:

4271

AN:

10542

Middle Eastern (MID)

AF:

0.490

AC:

144

AN:

294

European-Non Finnish (NFE)

AF:

0.374

AC:

25417

AN:

67932

Other (OTH)

AF:

0.457

AC:

963

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1868

3735

5603

7470

9338

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

630

1260

1890

2520

3150

<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:

0.397

Hom.:

25413

Bravo

AF:

0.463

TwinsUK

AF:

0.382

AC:

1416

ALSPAC

AF:

0.390

AC:

1504

ESP6500AA

AF:

0.568

AC:

2501

ESP6500EA

AF:

0.361

AC:

3106

ExAC

AF:

0.438

AC:

53190

Asia WGS

AF:

0.518

AC:

1803

AN:

3478

EpiCase

AF:

0.383

EpiControl

AF:

0.383

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 25, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 26715268) -

Pyle metaphyseal dysplasia

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

SFRP4-related disorder

Benign:1

Oct 17, 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

0.056

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.14

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.63

MetaRNN

Benign

0.000045

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.0

PhyloP100

0.43

PrimateAI

Benign

0.27

PROVEAN

Benign

0.34

REVEL

Benign

0.071

Sift

Benign

0.17

Sift4G

Benign

0.22

Polyphen

0.0

Vest4

0.036

MPC

0.42

ClinPred

0.0055

GERP RS

3.0

Varity_R

0.046

gMVP

0.17

Mutation Taster

=95/5

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

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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