Variant 7-37914238-C-T 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.567G>A(p.Thr189=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 1,612,808 control chromosomes in the GnomAD database, including 151,674 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 15387 hom., cov: 33)

Exomes 𝑓: 0.43 ( 136287 hom. )

Consequence

SFRP4
NM_003014.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -4.97

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=-0.65).

BP6

Variant 7-37914238-C-T is Benign according to our data. Variant chr7-37914238-C-T is described in ClinVar as [Benign]. Clinvar id is 1332948.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.97 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.621 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.567G>A	p.Thr189=	synonymous_variant	3/6	ENST00000436072.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFRP4	ENST00000436072.7 linkuse as main transcript	c.567G>A	p.Thr189=	synonymous_variant	3/6	1	NM_003014.4	P1
SFRP4	ENST00000447200.2 linkuse as main transcript	c.165G>A	p.Thr55=	synonymous_variant	4/6	5

Frequencies

GnomAD3 genomes

AF:

0.445

AC:

67626

AN:

151898

Hom.:

15364

Cov.:

show subpopulations

Gnomad AFR

AF:

0.472

Gnomad AMI

AF:

0.366

Gnomad AMR

AF:

0.481

Gnomad ASJ

AF:

0.419

Gnomad EAS

AF:

0.639

Gnomad SAS

AF:

0.596

Gnomad FIN

AF:

0.433

Gnomad MID

AF:

0.472

Gnomad NFE

AF:

0.400

Gnomad OTH

AF:

0.434

GnomAD3 exomes

AF:

0.460

AC:

115715

AN:

251382

Hom.:

27551

AF XY:

0.463

AC XY:

62859

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.481

Gnomad AMR exome

AF:

0.468

Gnomad ASJ exome

AF:

0.426

Gnomad EAS exome

AF:

0.636

Gnomad SAS exome

AF:

0.590

Gnomad FIN exome

AF:

0.422

Gnomad NFE exome

AF:

0.403

Gnomad OTH exome

AF:

0.434

GnomAD4 exome

AF:

0.428

AC:

625023

AN:

1460792

Hom.:

136287

Cov.:

AF XY:

0.432

AC XY:

313782

AN XY:

726760

show subpopulations

Gnomad4 AFR exome

AF:

0.479

Gnomad4 AMR exome

AF:

0.469

Gnomad4 ASJ exome

AF:

0.427

Gnomad4 EAS exome

AF:

0.618

Gnomad4 SAS exome

AF:

0.587

Gnomad4 FIN exome

AF:

0.423

Gnomad4 NFE exome

AF:

0.405

Gnomad4 OTH exome

AF:

0.432

GnomAD4 genome

AF:

0.445

AC:

67686

AN:

152016

Hom.:

15387

Cov.:

AF XY:

0.451

AC XY:

33555

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.472

Gnomad4 AMR

AF:

0.482

Gnomad4 ASJ

AF:

0.419

Gnomad4 EAS

AF:

0.639

Gnomad4 SAS

AF:

0.595

Gnomad4 FIN

AF:

0.433

Gnomad4 NFE

AF:

0.400

Gnomad4 OTH

AF:

0.439

Alfa

AF:

0.410

Hom.:

26744

Bravo

AF:

0.442

Asia WGS

AF:

0.592

AC:

2058

AN:

3478

EpiCase

AF:

0.405

EpiControl

AF:

0.406

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

-0.65

CADD

Benign

0.61

DANN

Benign

0.84

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