ENST00000447200.2:c.-52-38030C>G

Variant names:

• chr7-37964804-G-C
• rs1668357
• ENST00000447200.2:c.-52-38030C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000447200.2(SFRP4):​c.-52-38030C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0942 in 152,220 control chromosomes in the GnomAD database, including 849 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.094 (849 hom., cov: 31)
• Consequence: SFRP4 ENST00000447200.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140
• Publications: 13 publications found

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: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000447200.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFRP4	ENST00000447200.2	TSL:5	c.-52-38030C>G		intron	N/A	ENSP00000402262.2

Frequencies

GnomAD3 genomes AF: 0.0942 AC: 14324 AN: 152102 Hom.: 845 Cov.: 31

Gnomad AFR AF: 0.0208

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.109

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0942 AC: 14337 AN: 152220 Hom.: 849 Cov.: 31 AF XY: 0.0983 AC XY: 7313 AN XY: 74406

African (AFR) AF: 0.0208 AC: 862 AN: 41534

American (AMR) AF: 0.144 AC: 2202 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 459 AN: 3472

East Asian (EAS) AF: 0.114 AC: 586 AN: 5162

South Asian (SAS) AF: 0.115 AC: 557 AN: 4826

European-Finnish (FIN) AF: 0.146 AC: 1554 AN: 10614

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7740 AN: 68010

Other (OTH) AF: 0.110 AC: 232 AN: 2114

Alfa AF: 0.00269 Hom.: 81679

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.77
DANN	Benign	0.19
PhyloP100		-0.014

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1668357; hg19: chr7-38004406;