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GeneBe

8-41308972-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_003012.5(SFRP1):c.188C>T(p.Ala63Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SFRP1
NM_003012.5 missense

Scores

2
17

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.257
Variant links:
Genes affected
SFRP1 (HGNC:10776): (secreted frizzled related protein 1) This gene encodes a member of the SFRP family that contains a cysteine-rich domain homologous to the putative Wnt-binding site of Frizzled proteins. Members of this family act as soluble modulators of Wnt signaling; epigenetic silencing of SFRP genes leads to deregulated activation of the Wnt-pathway which is associated with cancer. This gene may also be involved in determining the polarity of photoreceptor cells in the retina. [provided by RefSeq, Sep 2009]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10569304).
BP6
Variant 8-41308972-G-A is Benign according to our data. Variant chr8-41308972-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2534539.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SFRP1NM_003012.5 linkuse as main transcriptc.188C>T p.Ala63Val missense_variant 1/3 ENST00000220772.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SFRP1ENST00000220772.8 linkuse as main transcriptc.188C>T p.Ala63Val missense_variant 1/31 NM_003012.5 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461094
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
726924
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsApr 07, 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
0.087
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
14
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.42
T
Eigen
Benign
-0.98
Eigen_PC
Benign
-0.97
FATHMM_MKL
Benign
0.14
N
LIST_S2
Benign
0.85
T
M_CAP
Benign
0.066
D
MetaRNN
Benign
0.11
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.48
N
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-1.6
N
REVEL
Benign
0.15
Sift
Benign
0.28
T
Sift4G
Benign
0.25
T
Polyphen
0.051
B
Vest4
0.084
MutPred
0.63
Loss of catalytic residue at A63 (P = 0.1061);
MVP
0.59
MPC
0.52
ClinPred
0.16
T
GERP RS
-4.5
Varity_R
0.033
gMVP
0.28

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-41166491; API