rs1721400

Variant names:

• chr7-38021183-T-C
• rs1721400
• ENST00000447200.2:c.-53+4127A>G

Variant summary

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

The ENST00000447200.2(SFRP4):​c.-53+4127A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.854 in 152,220 control chromosomes in the GnomAD database, including 55,828 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 0.85 (55828 hom., cov: 32)
• Consequence: SFRP4 ENST00000447200.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310
• Publications: 15 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

LOC105375236 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105375236	XR_001745170.2	n.1428+7602T>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFRP4	ENST00000447200.2	c.-53+4127A>G		intron_variant	Intron 1 of 5	5		ENSP00000402262.2

Frequencies

GnomAD3 genomes AF: 0.853 AC: 129817 AN: 152102 Hom.: 55779 Cov.: 32

Gnomad AFR AF: 0.936

Gnomad AMI AF: 0.843

Gnomad AMR AF: 0.743

Gnomad ASJ AF: 0.805

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.716

Gnomad FIN AF: 0.865

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.840

Gnomad OTH AF: 0.846

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

GnomAD4 genome AF: 0.854 AC: 129927 AN: 152220 Hom.: 55828 Cov.: 32 AF XY: 0.849 AC XY: 63211 AN XY: 74420

African (AFR) AF: 0.936 AC: 38881 AN: 41550

American (AMR) AF: 0.742 AC: 11345 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.805 AC: 2794 AN: 3470

East Asian (EAS) AF: 0.842 AC: 4366 AN: 5184

South Asian (SAS) AF: 0.716 AC: 3448 AN: 4816

European-Finnish (FIN) AF: 0.865 AC: 9158 AN: 10586

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.840 AC: 57135 AN: 68016

Other (OTH) AF: 0.847 AC: 1790 AN: 2114

Alfa AF: 0.843 Hom.: 199608

Bravo AF: 0.849

Asia WGS AF: 0.762 AC: 2647 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.5
DANN	Benign	0.52
PhyloP100		-0.031

Splicing

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

Other links and lift over

dbSNP: rs1721400; hg19: chr7-38060785;