rs7013229

Positions:

• chr8-41269833-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003012.5(SFRP1):​c.623-4344C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 152,082 control chromosomes in the GnomAD database, including 8,908 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 0.33 (8908 hom., cov: 32)
• Consequence: SFRP1 NM_003012.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

Genes affected

SFRP1 (HGNC:10776): (secreted frizzled related protein 1) This gene encodes a member of the SFRP family that contains a cysteine-rich domain homologous to the putative Wnt-binding site of Frizzled proteins. Members of this family act as soluble modulators of Wnt signaling; epigenetic silencing of SFRP genes leads to deregulated activation of the Wnt-pathway which is associated with cancer. This gene may also be involved in determining the polarity of photoreceptor cells in the retina. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFRP1	NM_003012.5	c.623-4344C>A		intron_variant		ENST00000220772.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFRP1	ENST00000220772.8	c.623-4344C>A		intron_variant		1	NM_003012.5	P1
SFRP1	ENST00000379845.3	c.215-4344C>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50805 AN: 151964 Hom.: 8909 Cov.: 32

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.0434

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.334 AC: 50845 AN: 152082 Hom.: 8908 Cov.: 32 AF XY: 0.329 AC XY: 24467 AN XY: 74346

Gnomad4 AFR AF: 0.316

Gnomad4 AMR AF: 0.260

Gnomad4 ASJ AF: 0.435

Gnomad4 EAS AF: 0.0435

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.385

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.344

Alfa AF: 0.361 Hom.: 1871

Bravo AF: 0.322

Asia WGS AF: 0.182 AC: 635 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.17
DANN	Benign	0.42

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

Publications

LitVar

Other links and lift over

dbSNP: rs7013229; hg19: chr8-41127352;