rs10488618

Variant names:

• chr7-37973596-C-T
• rs10488618
• ENST00000447200.2:c.-52-46822G>A

Variant summary

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

The ENST00000447200.2(SFRP4):​c.-52-46822G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0943 in 152,164 control chromosomes in the GnomAD database, including 812 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 (812 hom., cov: 32)
• Consequence: SFRP4 ENST00000447200.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.747
• Publications: 5 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFRP4	ENST00000447200.2	c.-52-46822G>A		intron_variant	Intron 1 of 5	5		ENSP00000402262.2

Frequencies

GnomAD3 genomes AF: 0.0942 AC: 14329 AN: 152046 Hom.: 808 Cov.: 32

Gnomad AFR AF: 0.0288

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.145

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.0943 AC: 14343 AN: 152164 Hom.: 812 Cov.: 32 AF XY: 0.0982 AC XY: 7304 AN XY: 74382

African (AFR) AF: 0.0288 AC: 1195 AN: 41534

American (AMR) AF: 0.141 AC: 2153 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 459 AN: 3470

East Asian (EAS) AF: 0.113 AC: 584 AN: 5176

South Asian (SAS) AF: 0.114 AC: 551 AN: 4822

European-Finnish (FIN) AF: 0.145 AC: 1540 AN: 10588

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

European-Non Finnish (NFE) AF: 0.110 AC: 7494 AN: 67986

Other (OTH) AF: 0.106 AC: 224 AN: 2114

Alfa AF: 0.103 Hom.: 113

Bravo AF: 0.0895

Asia WGS AF: 0.108 AC: 374 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	9.6
DANN	Benign	0.39
PhyloP100		0.75

Splicing

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

Other links and lift over

dbSNP: rs10488618; hg19: chr7-38013198;