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7-37907562-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

18

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]

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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 UniProt
SFRP4NM_003014.4 linkuse as main transcriptc.958C>A p.Pro320Thr missense_variant 6/6 ENST00000436072.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SFRP4ENST00000436072.7 linkuse as main transcriptc.958C>A p.Pro320Thr missense_variant 6/61 NM_003014.4 P1
SFRP4ENST00000478975.1 linkuse as main transcriptn.326C>A non_coding_transcript_exon_variant 2/22

Frequencies

GnomAD3 genomes
AF:
0.456
AC:
69168
AN:
151686
Hom.:
16558
Cov.:
32
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.:
35
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.:
32
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 submitterclinical testingInvitaeJan 31, 2024- -
Benign, criteria provided, single submitterclinical testingGeneDxFeb 25, 2021This variant is associated with the following publications: (PMID: 26715268) -
Pyle metaphyseal dysplasia Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 15, 2021- -
SFRP4-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 17, 2019This 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
T
BayesDel_noAF
Benign
-0.59
CADD
Benign
15
DANN
Benign
0.93
DEOGEN2
Benign
0.14
T
Eigen
Benign
-0.68
Eigen_PC
Benign
-0.50
FATHMM_MKL
Benign
0.38
N
LIST_S2
Benign
0.63
T
MetaRNN
Benign
0.000045
T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
0.0
N
MutationTaster
Benign
0.000045
P;P
PrimateAI
Benign
0.27
T
PROVEAN
Benign
0.34
N
REVEL
Benign
0.071
Sift
Benign
0.17
T
Sift4G
Benign
0.22
T
Polyphen
0.0
B
Vest4
0.036
MPC
0.42
ClinPred
0.0055
T
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.

Other links and lift over

dbSNP: rs1802073; hg19: chr7-37947164; COSMIC: COSV71412319; COSMIC: COSV71412319; API