chr7-38021183-T-C

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.

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.-53+4127A>G		intron	N/A	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 v4.9

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;