Variant 8-41309004-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_003012.5(SFRP1):c.156C>T(p.Tyr52Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00136 in 1,612,448 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0020 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 27 hom. )

Consequence

SFRP1
NM_003012.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.39

Variant links:

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]

SFRP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 8-41309004-G-A is Benign according to our data. Variant chr8-41309004-G-A is described in ClinVar as [Benign]. Clinvar id is 771425.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.39 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00129 (1883/1460130) while in subpopulation AMR AF= 0.0289 (1293/44714). AF 95% confidence interval is 0.0276. There are 27 homozygotes in gnomad4_exome. There are 833 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 309 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFRP1	NM_003012.5 linkuse as main transcript	c.156C>T	p.Tyr52Tyr	synonymous_variant	1/3	ENST00000220772.8	NP_003003.3	Q8N474

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFRP1	ENST00000220772.8 linkuse as main transcript	c.156C>T	p.Tyr52Tyr	synonymous_variant	1/3	1	NM_003012.5	ENSP00000220772.3		Q8N474

Frequencies

GnomAD3 genomes

AF:

0.00200

AC:

304

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0152

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00775

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00490

AC:

1217

AN:

248148

Hom.:

AF XY:

0.00373

AC XY:

502

AN XY:

134742

show subpopulations

Gnomad AFR exome

AF:

0.000186

Gnomad AMR exome

AF:

0.0296

Gnomad ASJ exome

AF:

0.000199

Gnomad EAS exome

AF:

0.00803

Gnomad SAS exome

AF:

0.000621

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000888

Gnomad OTH exome

AF:

0.00247

GnomAD4 exome

AF:

0.00129

AC:

1883

AN:

1460130

Hom.:

Cov.:

AF XY:

0.00115

AC XY:

833

AN XY:

726524

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.0289

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.0106

Gnomad4 SAS exome

AF:

0.000719

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000306

Gnomad4 OTH exome

AF:

0.00103

GnomAD4 genome

AF:

0.00203

AC:

309

AN:

152318

Hom.:

Cov.:

AF XY:

0.00216

AC XY:

161

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.0155

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00777

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.000690

Hom.:

Bravo

AF:

0.00354

Asia WGS

AF:

0.00577

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

0.97

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over