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GeneBe

7-37907501-C-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.1019G>A(p.Arg340Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 1,611,698 control chromosomes in the GnomAD database, including 36,456 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 0.24 ( 4872 hom., cov: 32)
Exomes 𝑓: 0.20 ( 31584 hom. )

Consequence

SFRP4
NM_003014.4 missense

Scores

18

Clinical Significance

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

Conservation

PhyloP100: 0.695
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=0.003261745).
BP6
Variant 7-37907501-C-T is Benign according to our data. Variant chr7-37907501-C-T is described in ClinVar as [Benign]. Clinvar id is 1332946.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SFRP4NM_003014.4 linkuse as main transcriptc.1019G>A p.Arg340Lys missense_variant 6/6 ENST00000436072.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SFRP4ENST00000436072.7 linkuse as main transcriptc.1019G>A p.Arg340Lys missense_variant 6/61 NM_003014.4 P1
SFRP4ENST00000478975.1 linkuse as main transcriptn.387G>A non_coding_transcript_exon_variant 2/22

Frequencies

GnomAD3 genomes
AF:
0.242
AC:
36804
AN:
151968
Hom.:
4866
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.348
Gnomad AMI
AF:
0.170
Gnomad AMR
AF:
0.161
Gnomad ASJ
AF:
0.206
Gnomad EAS
AF:
0.245
Gnomad SAS
AF:
0.130
Gnomad FIN
AF:
0.259
Gnomad MID
AF:
0.304
Gnomad NFE
AF:
0.204
Gnomad OTH
AF:
0.233
GnomAD3 exomes
AF:
0.198
AC:
49610
AN:
250532
Hom.:
5515
AF XY:
0.196
AC XY:
26499
AN XY:
135420
show subpopulations
Gnomad AFR exome
AF:
0.353
Gnomad AMR exome
AF:
0.0997
Gnomad ASJ exome
AF:
0.216
Gnomad EAS exome
AF:
0.246
Gnomad SAS exome
AF:
0.133
Gnomad FIN exome
AF:
0.246
Gnomad NFE exome
AF:
0.205
Gnomad OTH exome
AF:
0.199
GnomAD4 exome
AF:
0.204
AC:
298058
AN:
1459612
Hom.:
31584
Cov.:
32
AF XY:
0.203
AC XY:
147216
AN XY:
726192
show subpopulations
Gnomad4 AFR exome
AF:
0.346
Gnomad4 AMR exome
AF:
0.105
Gnomad4 ASJ exome
AF:
0.218
Gnomad4 EAS exome
AF:
0.240
Gnomad4 SAS exome
AF:
0.135
Gnomad4 FIN exome
AF:
0.244
Gnomad4 NFE exome
AF:
0.205
Gnomad4 OTH exome
AF:
0.206
GnomAD4 genome
AF:
0.242
AC:
36839
AN:
152086
Hom.:
4872
Cov.:
32
AF XY:
0.241
AC XY:
17894
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.347
Gnomad4 AMR
AF:
0.161
Gnomad4 ASJ
AF:
0.206
Gnomad4 EAS
AF:
0.246
Gnomad4 SAS
AF:
0.130
Gnomad4 FIN
AF:
0.259
Gnomad4 NFE
AF:
0.204
Gnomad4 OTH
AF:
0.236
Alfa
AF:
0.210
Hom.:
7415
Bravo
AF:
0.240
TwinsUK
AF:
0.212
AC:
786
ALSPAC
AF:
0.210
AC:
810
ESP6500AA
AF:
0.341
AC:
1503
ESP6500EA
AF:
0.192
AC:
1651
ExAC
AF:
0.203
AC:
24597
Asia WGS
AF:
0.175
AC:
608
AN:
3478
EpiCase
AF:
0.211
EpiControl
AF:
0.210

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 submitterclinical testingGenome-Nilou LabJul 15, 2021- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 31, 2024- -
SFRP4-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesOct 21, 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
0.066
BayesDel_addAF
Benign
-0.74
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
4.3
DANN
Benign
0.72
DEOGEN2
Benign
0.15
T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.064
N
LIST_S2
Benign
0.46
T
MetaRNN
Benign
0.0033
T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
0.0
N
MutationTaster
Benign
1.0
P;P
PrimateAI
Benign
0.25
T
PROVEAN
Benign
0.020
N
REVEL
Benign
0.086
Sift
Benign
0.86
T
Sift4G
Benign
0.52
T
Polyphen
0.0
B
Vest4
0.010
MPC
0.38
ClinPred
0.000014
T
GERP RS
0.88
Varity_R
0.031
gMVP
0.13

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: rs1802074; hg19: chr7-37947103; COSMIC: COSV71412323; COSMIC: COSV71412323; API