Variant rs1132553 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003014.4(SFRP4):c.786C>T(p.Arg262=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 1,611,562 control chromosomes in the GnomAD database, including 262,640 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.54 ( 22554 hom., cov: 32)

Exomes 𝑓: 0.57 ( 240086 hom. )

Consequence

SFRP4
NM_003014.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.268

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 7-37912124-G-A is Benign according to our data. Variant chr7-37912124-G-A is described in ClinVar as [Benign]. Clinvar id is 1332947.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.268 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFRP4	NM_003014.4 linkuse as main transcript	c.786C>T	p.Arg262=	synonymous_variant	4/6	ENST00000436072.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFRP4	ENST00000436072.7 linkuse as main transcript	c.786C>T	p.Arg262=	synonymous_variant	4/6	1	NM_003014.4	P1
SFRP4	ENST00000447200.2 linkuse as main transcript	c.384C>T	p.Arg128=	synonymous_variant	5/6	5

Frequencies

GnomAD3 genomes

AF:

0.540

AC:

82006

AN:

151834

Hom.:

22535

Cov.:

show subpopulations

Gnomad AFR

AF:

0.478

Gnomad AMI

AF:

0.634

Gnomad AMR

AF:

0.512

Gnomad ASJ

AF:

0.580

Gnomad EAS

AF:

0.362

Gnomad SAS

AF:

0.397

Gnomad FIN

AF:

0.569

Gnomad MID

AF:

0.509

Gnomad NFE

AF:

0.600

Gnomad OTH

AF:

0.549

GnomAD3 exomes

AF:

0.535

AC:

134352

AN:

251252

Hom.:

36874

AF XY:

0.533

AC XY:

72403

AN XY:

135782

show subpopulations

Gnomad AFR exome

AF:

0.468

Gnomad AMR exome

AF:

0.528

Gnomad ASJ exome

AF:

0.572

Gnomad EAS exome

AF:

0.363

Gnomad SAS exome

AF:

0.404

Gnomad FIN exome

AF:

0.578

Gnomad NFE exome

AF:

0.596

Gnomad OTH exome

AF:

0.563

GnomAD4 exome

AF:

0.570

AC:

832199

AN:

1459610

Hom.:

240086

Cov.:

AF XY:

0.566

AC XY:

411254

AN XY:

726188

show subpopulations

Gnomad4 AFR exome

AF:

0.471

Gnomad4 AMR exome

AF:

0.527

Gnomad4 ASJ exome

AF:

0.571

Gnomad4 EAS exome

AF:

0.382

Gnomad4 SAS exome

AF:

0.408

Gnomad4 FIN exome

AF:

0.577

Gnomad4 NFE exome

AF:

0.595

Gnomad4 OTH exome

AF:

0.564

GnomAD4 genome

AF:

0.540

AC:

82057

AN:

151952

Hom.:

22554

Cov.:

AF XY:

0.533

AC XY:

39620

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.478

Gnomad4 AMR

AF:

0.511

Gnomad4 ASJ

AF:

0.580

Gnomad4 EAS

AF:

0.361

Gnomad4 SAS

AF:

0.397

Gnomad4 FIN

AF:

0.569

Gnomad4 NFE

AF:

0.600

Gnomad4 OTH

AF:

0.545

Alfa

AF:

0.585

Hom.:

54225

Bravo

AF:

0.541

Asia WGS

AF:

0.400

AC:

1390

AN:

3478

EpiCase

AF:

0.594

EpiControl

AF:

0.593

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Pyle metaphyseal dysplasia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

SFRP4-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

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

BayesDel_noAF

Benign

-0.52

CADD

Benign

5.8

DANN

Benign

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over