rs1132552

Variant names:

• chr7-37914238-C-G
• rs1132552
• NM_003014.4:c.567G>C

Your query was ambiguous. Multiple possible variants found:

• chr7-37914238-C-G
• chr7-37914238-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_003014.4(SFRP4):​c.567G>C​(p.Thr189Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T189T) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SFRP4 NM_003014.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.97
• Publications: 26 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

ENSG00000290149 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP7: Synonymous conserved (PhyloP=-4.97 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFRP4	NM_003014.4	MANE Select	c.567G>C	p.Thr189Thr	synonymous	Exon 3 of 6	NP_003005.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFRP4	ENST00000436072.7	TSL:1 MANE Select	c.567G>C	p.Thr189Thr	synonymous	Exon 3 of 6	ENSP00000410715.2
	ENSG00000290149	ENST00000476620.1	TSL:4	c.-37-34602C>G		intron	N/A	ENSP00000425858.1
	SFRP4	ENST00000447200.2	TSL:5	c.165G>C	p.Thr55Thr	synonymous	Exon 4 of 6	ENSP00000402262.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 41172

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.35
DANN	Benign	0.71
PhyloP100		-5.0

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

Other links and lift over

dbSNP: rs1132552; hg19: chr7-37953840;