8-41261978-T-C

Variant names:

• chr8-41261978-T-C
• rs4736958
• NM_003012.5:c.*3189A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003012.5. 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
	SFRP1	NM_003012.5	MANE Select	c.*3189A>G		3_prime_UTR	Exon 3 of 3	NP_003003.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFRP1	ENST00000220772.8	TSL:1 MANE Select	c.*3189A>G		3_prime_UTR	Exon 3 of 3	ENSP00000220772.3
	SFRP1	ENST00000379845.3	TSL:2	c.*3189A>G		3_prime_UTR	Exon 3 of 3	ENSP00000369174.3

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.00806 AC: 335 AN: 41554

American (AMR) AF: 0.159 AC: 2425 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 40 AN: 3470

East Asian (EAS) AF: 0.299 AC: 1549 AN: 5182

South Asian (SAS) AF: 0.168 AC: 810 AN: 4824

European-Finnish (FIN) AF: 0.0304 AC: 323 AN: 10610

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0116 AC: 786 AN: 68018

Other (OTH) AF: 0.0397 AC: 84 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	18
DANN	Benign	0.91
PhyloP100		4.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4736958; hg19: chr8-41119497;