7-37918687-G-A

Variant names:

• chr7-37918687-G-A
• rs1376264
• ENST00000476620.1:c.-37-30153G>A

Variant summary

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

The ENST00000476620.1(ENSG00000290149):​c.-37-30153G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 151,972 control chromosomes in the GnomAD database, including 5,043 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 0.25 (5043 hom., cov: 32)
• Consequence: ENSG00000290149 ENST00000476620.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135
• Publications: 9 publications found

Genes affected

ENSG00000290149 (HGNC:):

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000476620.1. 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
	ENSG00000290149	ENST00000476620.1	TSL:4	c.-37-30153G>A		intron	N/A	ENSP00000425858.1
	SFRP4	ENST00000447200.2	TSL:5	c.44-4234C>T		intron	N/A	ENSP00000402262.2

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37368 AN: 151854 Hom.: 5037 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.246 AC: 37384 AN: 151972 Hom.: 5043 Cov.: 32 AF XY: 0.244 AC XY: 18128 AN XY: 74274

African (AFR) AF: 0.148 AC: 6115 AN: 41448

American (AMR) AF: 0.198 AC: 3028 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 985 AN: 3466

East Asian (EAS) AF: 0.174 AC: 902 AN: 5174

South Asian (SAS) AF: 0.189 AC: 908 AN: 4794

European-Finnish (FIN) AF: 0.325 AC: 3433 AN: 10550

Middle Eastern (MID) AF: 0.290 AC: 84 AN: 290

European-Non Finnish (NFE) AF: 0.309 AC: 21009 AN: 67952

Other (OTH) AF: 0.244 AC: 514 AN: 2108

Alfa AF: 0.290 Hom.: 28419

Bravo AF: 0.233

Asia WGS AF: 0.185 AC: 644 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.88
DANN	Benign	0.71
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1376264; hg19: chr7-37958289;