rs4736958

chr8-41261978-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003012.5(SFRP1):c.*3189A>G variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0418 in 152,272 control chromosomes in the GnomAD database, including 579 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 0.042 (579 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SFRP1 NM_003012.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.33

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SFRP1	NM_003012.5	c.*3189A>G		3_prime_UTR_variant	3/3	ENST00000220772.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SFRP1	ENST00000220772.8	c.*3189A>G		3_prime_UTR_variant	3/3	1	NM_003012.5	P1
SFRP1	ENST00000379845.3	c.*3189A>G		3_prime_UTR_variant	3/3	2

Frequencies

GnomAD3 genomes AF: 0.0417 AC: 6349 AN: 152154 Hom.: 578 Cov.: 32

Gnomad AFR AF: 0.00809

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.0304

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0115

Gnomad OTH AF: 0.0402

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 32 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 18

Gnomad4 FIN exome AF: 0.00

GnomAD4 genome AF: 0.0418 AC: 6362 AN: 152272 Hom.: 579 Cov.: 32 AF XY: 0.0488 AC XY: 3635 AN XY: 74452

Gnomad4 AFR AF: 0.00806

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.0115

Gnomad4 EAS AF: 0.299

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.0304

Gnomad4 NFE AF: 0.0116

Gnomad4 OTH AF: 0.0397

Alfa AF: 0.0205 Hom.: 33

Bravo AF: 0.0487

Asia WGS AF: 0.224 AC: 776 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
Cadd	Benign	18
Dann	Benign	0.91

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: rs4736958; hg19: chr8-41119497;