rs62443106

Variant names:

• chr7-37917102-C-A
• rs62443106
• ENST00000476620.1:c.-37-31738C>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000476620.1(ENSG00000290149):​c.-37-31738C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0281 in 152,262 control chromosomes in the GnomAD database, including 98 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 0.028 (98 hom., cov: 32)
• Consequence: ENSG00000290149 ENST00000476620.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.882
• Publications: 2 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: PanelApp Australia, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0809 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000290149	ENST00000476620.1	TSL:4	c.-37-31738C>A		intron	N/A	ENSP00000425858.1	D6RIH7
	SFRP4	ENST00000447200.2	TSL:5	c.44-2649G>T		intron	N/A	ENSP00000402262.2	C9JMJ2
	SFRP4	ENST00000960683.1		c.-565G>T		upstream_gene	N/A	ENSP00000630742.1

Frequencies

GnomAD3 genomes AF: 0.0281 AC: 4274 AN: 152144 Hom.: 97 Cov.: 32

Gnomad AFR AF: 0.0281

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0179

Gnomad ASJ AF: 0.00980

Gnomad EAS AF: 0.0873

Gnomad SAS AF: 0.0695

Gnomad FIN AF: 0.0254

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0246

Gnomad OTH AF: 0.0239

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

GnomAD4 genome AF: 0.0281 AC: 4277 AN: 152262 Hom.: 98 Cov.: 32 AF XY: 0.0293 AC XY: 2183 AN XY: 74454

African (AFR) AF: 0.0281 AC: 1167 AN: 41540

American (AMR) AF: 0.0178 AC: 273 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00980 AC: 34 AN: 3470

East Asian (EAS) AF: 0.0875 AC: 454 AN: 5186

South Asian (SAS) AF: 0.0692 AC: 334 AN: 4828

European-Finnish (FIN) AF: 0.0254 AC: 270 AN: 10614

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0246 AC: 1671 AN: 68010

Other (OTH) AF: 0.0256 AC: 54 AN: 2112

Alfa AF: 0.0237 Hom.: 6

Bravo AF: 0.0273

Asia WGS AF: 0.0780 AC: 271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	13
DANN	Benign	0.85
PhyloP100		0.88
PromoterAI		0.034	Neutral
Mutation Taster		=91/9	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs62443106;

hg19: chr7-37956704;