dbSNP rs765603358: SFRP1:p.Val312Met (chr8-41265178-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_003012.5(SFRP1):c.934G>A(p.Val312Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,314,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000044 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

SFRP1
NM_003012.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.52

Publications

1 publications found

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]

SFRP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.274341).

BS2

High AC in GnomAd4 at 6 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003012.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFRP1	NM_003012.5	MANE Select	c.934G>A	p.Val312Met	missense	Exon 3 of 3	NP_003003.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SFRP1	ENST00000220772.8	TSL:1 MANE Select	c.934G>A	p.Val312Met	missense	Exon 3 of 3	ENSP00000220772.3	Q8N474
SFRP1	ENST00000923189.1		c.856G>A	p.Val286Met	missense	Exon 2 of 2	ENSP00000593248.1
SFRP1	ENST00000379845.3	TSL:2	c.526G>A	p.Val176Met	missense	Exon 3 of 3	ENSP00000369174.3	Q6ZSL4

Frequencies

GnomAD3 genomes

AF:

0.0000440

AC:

AN:

136216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000125

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000157

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000254

AC:

AN:

236400

AF XY:

0.0000235

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000571

Gnomad FIN exome

AF:

0.0000960

Gnomad NFE exome

AF:

0.00000952

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000178

AC:

AN:

1178692

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

582388

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25468

American (AMR)

AF:

0.00

AC:

AN:

35158

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16306

East Asian (EAS)

AF:

0.000127

AC:

AN:

15790

South Asian (SAS)

AF:

0.0000375

AC:

AN:

80038

European-Finnish (FIN)

AF:

0.0000319

AC:

AN:

31318

Middle Eastern (MID)

AF:

0.000234

AC:

AN:

4280

European-Non Finnish (NFE)

AF:

0.0000151

AC:

AN:

927872

Other (OTH)

AF:

0.00

AC:

AN:

42462

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000440

AC:

AN:

136216

Hom.:

Cov.:

AF XY:

0.0000153

AC XY:

AN XY:

65438

show subpopulations

African (AFR)

AF:

0.000106

AC:

AN:

37606

American (AMR)

AF:

0.00

AC:

AN:

13100

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3296

East Asian (EAS)

AF:

0.00

AC:

AN:

3802

South Asian (SAS)

AF:

0.00

AC:

AN:

3712

European-Finnish (FIN)

AF:

0.000125

AC:

AN:

7972

Middle Eastern (MID)

AF:

0.00

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.0000157

AC:

AN:

63684

Other (OTH)

AF:

0.00

AC:

AN:

1902

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.567

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000602

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000247

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.34

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.53

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.047

MetaRNN

Benign

0.27

MetaSVM

Benign

-0.51

MutationAssessor

Benign

1.6

PhyloP100

2.5

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.68

REVEL

Benign

0.16

Sift

Uncertain

0.021

Sift4G

Uncertain

0.031

Polyphen

0.99

Vest4

0.41

MutPred

0.18

Gain of disorder (P = 0.0547)

MVP

0.80

MPC

0.66

ClinPred

0.25

GERP RS

4.9

Varity_R

0.073

gMVP

0.69

Mutation Taster

=83/17

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over