8-41309155-C-T

Variant names:

• chr8-41309155-C-T
• rs62636770
• NM_003012.5:c.5G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003012.5(SFRP1):​c.5G>A​(p.Gly2Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000803 in 1,245,328 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: SFRP1 NM_003012.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.300

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25716114).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFRP1	NM_003012.5	c.5G>A	p.Gly2Asp	missense_variant	Exon 1 of 3	ENST00000220772.8	NP_003003.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFRP1	ENST00000220772.8	c.5G>A	p.Gly2Asp	missense_variant	Exon 1 of 3	1	NM_003012.5	ENSP00000220772.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.03e-7 AC: 1 AN: 1245328 Hom.: 0 Cov.: 32 AF XY: 0.00000164 AC XY: 1 AN XY: 609636

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.78e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.24	T
M_CAP	Pathogenic	0.55	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.0	N
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.45	N
REVEL	Benign	0.071
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.21	T
Polyphen		0.028	B
Vest4		0.15
MutPred		0.30		Loss of MoRF binding (P = 0.027);
MVP		0.63
MPC		1.6
ClinPred		0.36	T
GERP RS		2.4
Varity_R		0.15
gMVP		0.81

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: rs62636770; hg19: chr8-41166674;