Menu
GeneBe

7-37907636-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1

The NM_003014.4(SFRP4):c.884G>A(p.Arg295Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,612,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

SFRP4
NM_003014.4 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.33
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.019672394).
BP6
Variant 7-37907636-C-T is Benign according to our data. Variant chr7-37907636-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3160908.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0000137 (20/1459720) while in subpopulation MID AF= 0.000182 (1/5502). AF 95% confidence interval is 0.0000652. There are 0 homozygotes in gnomad4_exome. There are 14 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SFRP4NM_003014.4 linkuse as main transcriptc.884G>A p.Arg295Gln missense_variant 6/6 ENST00000436072.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SFRP4ENST00000436072.7 linkuse as main transcriptc.884G>A p.Arg295Gln missense_variant 6/61 NM_003014.4 P1
SFRP4ENST00000478975.1 linkuse as main transcriptn.252G>A non_coding_transcript_exon_variant 2/22

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152172
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000241
AC:
6
AN:
248948
Hom.:
0
AF XY:
0.0000297
AC XY:
4
AN XY:
134550
show subpopulations
Gnomad AFR exome
AF:
0.0000617
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000164
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000177
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000137
AC:
20
AN:
1459720
Hom.:
0
Cov.:
31
AF XY:
0.0000193
AC XY:
14
AN XY:
726090
show subpopulations
Gnomad4 AFR exome
AF:
0.0000900
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000151
Gnomad4 SAS exome
AF:
0.0000117
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000630
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152290
Hom.:
0
Cov.:
32
AF XY:
0.0000537
AC XY:
4
AN XY:
74464
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000573
Hom.:
0
Bravo
AF:
0.0000567
ExAC
AF:
0.0000247
AC:
3
EpiCase
AF:
0.000109
EpiControl
AF:
0.0000593

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsSep 29, 2023This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.062
BayesDel_addAF
Benign
-0.53
T
BayesDel_noAF
Benign
-0.73
CADD
Benign
3.1
DANN
Benign
0.82
DEOGEN2
Benign
0.14
T
Eigen
Benign
-1.6
Eigen_PC
Benign
-1.7
FATHMM_MKL
Benign
0.0080
N
LIST_S2
Benign
0.72
T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.020
T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
-0.20
N
MutationTaster
Benign
0.87
D;N
PrimateAI
Benign
0.22
T
PROVEAN
Benign
0.13
N
REVEL
Benign
0.059
Sift
Benign
0.48
T
Sift4G
Benign
0.40
T
Polyphen
0.0
B
Vest4
0.026
MVP
0.42
MPC
0.43
ClinPred
0.021
T
GERP RS
-10
Varity_R
0.041
gMVP
0.090

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: rs568754305; hg19: chr7-37947238; COSMIC: COSV71412719; COSMIC: COSV71412719; API