dbSNP rs184528079: SFRP1:p.Tyr52Tyr (chr8-41309004-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

2 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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. GnomAdExome4 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 GnomAdExome4. There are 833 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High AC in GnomAd4 at 309 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFRP1	NM_003012.5	MANE Select	c.156C>T	p.Tyr52Tyr	synonymous	Exon 1 of 3	NP_003003.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFRP1	ENST00000220772.8	TSL:1 MANE Select	c.156C>T	p.Tyr52Tyr	synonymous	Exon 1 of 3	ENSP00000220772.3	Q8N474
	SFRP1	ENST00000923189.1		c.156C>T	p.Tyr52Tyr	synonymous	Exon 1 of 2	ENSP00000593248.1

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

GnomAD2 exomes

AF:

0.00490

AC:

1217

AN:

248148

AF XY:

0.00373

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 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

African (AFR)

AF:

0.000239

AC:

AN:

33476

American (AMR)

AF:

0.0289

AC:

1293

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.000153

AC:

AN:

26130

East Asian (EAS)

AF:

0.0106

AC:

419

AN:

39688

South Asian (SAS)

AF:

0.000719

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51834

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000306

AC:

AN:

1111900

Other (OTH)

AF:

0.00103

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

112

223

335

446

558

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00203

AC:

309

AN:

152318

Hom.:

Cov.:

AF XY:

0.00216

AC XY:

161

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.000337

AC:

AN:

41590

American (AMR)

AF:

0.0155

AC:

238

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00777

AC:

AN:

5148

South Asian (SAS)

AF:

0.00104

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68024

Other (OTH)

AF:

0.00236

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Uncertain

0.97

PhyloP100

1.4

PromoterAI

-0.033

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over