Genetic Variant SFRP2:p.Leu82Leu (chr4-153788590-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_003013.3(SFRP2):c.246G>A(p.Leu82Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00153 in 1,614,162 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0083 ( 17 hom., cov: 33)

Exomes 𝑓: 0.00082 ( 15 hom. )

Consequence

SFRP2
NM_003013.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.239

Variant links:

Genes affected

SFRP2 (HGNC:10777): (secreted frizzled related protein 2) 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. SFRPs act as soluble modulators of Wnt signaling. Methylation of this gene is a potential marker for the presence of colorectal cancer. [provided by RefSeq, Jul 2008]

SFRP2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 4-153788590-C-T is Benign according to our data. Variant chr4-153788590-C-T is described in ClinVar as [Benign]. Clinvar id is 776025.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.239 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00827 (1259/152290) while in subpopulation AFR AF = 0.0286 (1189/41574). AF 95% confidence interval is 0.0272. There are 17 homozygotes in GnomAd4. There are 593 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position FAILED quality control check.

BS2

High AC in GnomAd4 at 1259 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFRP2	NM_003013.3 link	c.246G>A	p.Leu82Leu	synonymous_variant	Exon 1 of 3	ENST00000274063.5	NP_003004.1	Q96HF1A0A140VJU3B3KSM5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFRP2	ENST00000274063.5 link	c.246G>A	p.Leu82Leu	synonymous_variant	Exon 1 of 3	1	NM_003013.3	ENSP00000274063.4		Q96HF1

Frequencies

GnomAD3 genomes

AF:

0.00825

AC:

1256

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0286

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00301

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00766

GnomAD2 exomes

AF:

0.00208

AC:

524

AN:

251362

AF XY:

0.00152

show subpopulations

Gnomad AFR exome

AF:

0.0285

Gnomad AMR exome

AF:

0.00130

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000968

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000825

AC:

1206

AN:

1461872

Hom.:

Cov.:

AF XY:

0.000712

AC XY:

518

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.0289

AC:

966

AN:

33480

Gnomad4 AMR exome

AF:

0.00141

AC:

AN:

44724

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

26136

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39700

Gnomad4 SAS exome

AF:

0.0000580

AC:

AN:

86258

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

53414

Gnomad4 NFE exome

AF:

0.0000450

AC:

AN:

1111996

Gnomad4 Remaining exome

AF:

0.00194

AC:

117

AN:

60396

Heterozygous variant carriers

155

232

310

387

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

108

144

180

<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:

0.00827

AC:

1259

AN:

152290

Hom.:

Cov.:

AF XY:

0.00796

AC XY:

593

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0286

AC:

0.0285996

AN:

0.0285996

Gnomad4 AMR

AF:

0.00301

AC:

0.00300654

AN:

0.00300654

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.000118

AC:

0.000117626

AN:

0.000117626

Gnomad4 OTH

AF:

0.00758

AC:

0.00758294

AN:

0.00758294

Heterozygous variant carriers

116

175

233

291

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00285

Hom.:

Bravo

AF:

0.00948

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 29, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

9.5

DANN

Benign

0.91

Mutation Taster

=94/6

polymorphism

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