dbSNP rs1554369743: SFRP4:p.Asp278Glu (chr7-37909638-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003014.4(SFRP4):c.834T>G(p.Asp278Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,428,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SFRP4
NM_003014.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.568

Publications

0 publications found

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]

SFRP4 Gene-Disease associations (from GenCC):

Pyle disease
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)

SFRP4 links:

ENSG00000290149 (HGNC:):

ENSG00000290149 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15018427).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003014.4. 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
	SFRP4	NM_003014.4	MANE Select	c.834T>G	p.Asp278Glu	missense	Exon 5 of 6	NP_003005.2	Q6FHJ7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SFRP4	ENST00000436072.7	TSL:1 MANE Select	c.834T>G	p.Asp278Glu	missense	Exon 5 of 6	ENSP00000410715.2	Q6FHJ7
ENSG00000290149	ENST00000476620.1	TSL:4	c.-37-39202A>C		intron	N/A	ENSP00000425858.1	D6RIH7
SFRP4	ENST00000960684.1		c.834T>G	p.Asp278Glu	missense	Exon 5 of 6	ENSP00000630743.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000140

AC:

AN:

1428842

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

710490

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32198

American (AMR)

AF:

0.00

AC:

AN:

41226

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25650

East Asian (EAS)

AF:

0.00

AC:

AN:

38054

South Asian (SAS)

AF:

0.00

AC:

AN:

80136

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52808

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5688

European-Non Finnish (NFE)

AF:

0.00000183

AC:

AN:

1094134

Other (OTH)

AF:

0.00

AC:

AN:

58948

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.16

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.65

M_CAP

Benign

0.0055

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.46

PhyloP100

-0.57

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.0

REVEL

Benign

0.048

Sift

Benign

0.095

Sift4G

Benign

0.19

Polyphen

0.0020

Vest4

0.26

MutPred

0.45

Loss of sheet (P = 0.0457)

MVP

0.42

MPC

0.36

ClinPred

0.15

GERP RS

-7.3

Varity_R

0.057

gMVP

0.27

Mutation Taster

=73/27

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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