rs16890444

Variant names:

• chr8-41301885-C-T
• rs16890444
• NM_003012.5:c.622+1576G>A

Variant summary

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

The NM_003012.5(SFRP1):​c.622+1576G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,156 control chromosomes in the GnomAD database, including 1,441 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 0.11 (1441 hom., cov: 32)
• Consequence: SFRP1 NM_003012.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.95
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFRP1	NM_003012.5	c.622+1576G>A		intron_variant	Intron 2 of 2	ENST00000220772.8	NP_003003.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFRP1	ENST00000220772.8	c.622+1576G>A		intron_variant	Intron 2 of 2	1	NM_003012.5	ENSP00000220772.3
SFRP1	ENST00000379845.3	c.214+1576G>A		intron_variant	Intron 2 of 2	2		ENSP00000369174.3

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17136 AN: 152038 Hom.: 1434 Cov.: 32

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.0602

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.0626

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0482

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.113 AC: 17148 AN: 152156 Hom.: 1441 Cov.: 32 AF XY: 0.116 AC XY: 8642 AN XY: 74396

African (AFR) AF: 0.187 AC: 7760 AN: 41478

American (AMR) AF: 0.204 AC: 3124 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0602 AC: 209 AN: 3470

East Asian (EAS) AF: 0.180 AC: 929 AN: 5164

South Asian (SAS) AF: 0.195 AC: 940 AN: 4820

European-Finnish (FIN) AF: 0.0626 AC: 663 AN: 10596

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0483 AC: 3282 AN: 68014

Other (OTH) AF: 0.101 AC: 213 AN: 2114

Alfa AF: 0.0775 Hom.: 1140

Bravo AF: 0.122

Asia WGS AF: 0.197 AC: 686 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.086
DANN	Benign	0.66
PhyloP100		-2.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs16890444; hg19: chr8-41159404;