7-37907562-G-T

Position:

chr7-37907562-G-T

Variant summary

Our verdict is Benign. Variant got -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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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:

ENSG00000290149 (HGNC:):

ENSG00000290149 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 ClinVar 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/exons	MANE	Protein	UniProt
SFRP4	NM_003014.4 linkuse as main transcript	c.958C>A	p.Pro320Thr	missense_variant	6/6	ENST00000436072.7	NP_003005.2	Q6FHJ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SFRP4	ENST00000436072.7 linkuse as main transcript	c.958C>A	p.Pro320Thr	missense_variant	6/6	1	NM_003014.4	ENSP00000410715.2	Q6FHJ7
ENSG00000290149	ENST00000476620.1 linkuse as main transcript	c.-37-41278G>T		intron_variant		4		ENSP00000425858.1	D6RIH7
SFRP4	ENST00000478975.1 linkuse as main transcript	n.326C>A		non_coding_transcript_exon_variant	2/2	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

GnomAD3 exomes

AF:

0.437

AC:

109702

AN:

251174

Hom.:

24781

AF XY:

0.435

AC XY:

59036

AN XY:

135740

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 SAS exome

AF:

0.524

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

Gnomad4 AFR exome

AF:

0.579

Gnomad4 AMR exome

AF:

0.466

Gnomad4 ASJ exome

AF:

0.424

Gnomad4 EAS exome

AF:

0.524

Gnomad4 SAS exome

AF:

0.522

Gnomad4 FIN exome

AF:

0.394

Gnomad4 NFE exome

AF:

0.376

Gnomad4 OTH exome

AF:

0.414

GnomAD4 genome

AF:

0.456

AC:

69240

AN:

151804

Hom.:

16582

Cov.:

AF XY:

0.460

AC XY:

34099

AN XY:

74178

show subpopulations

Gnomad4 AFR

AF:

0.577

Gnomad4 AMR

AF:

0.491

Gnomad4 ASJ

AF:

0.411

Gnomad4 EAS

AF:

0.551

Gnomad4 SAS

AF:

0.526

Gnomad4 FIN

AF:

0.405

Gnomad4 NFE

AF:

0.374

Gnomad4 OTH

AF:

0.457

Alfa

AF:

0.381

Hom.:

15864

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 25, 2021	This variant is associated with the following publications: (PMID: 26715268) -

Pyle metaphyseal dysplasia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

SFRP4-related disorder

Benign:1

Benign, no assertion criteria provided

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

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

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

MutationTaster

Benign

0.000045

P;P

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

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