8-41309004-G-A

Variant names:

• chr8-41309004-G-A
• rs184528079
• NM_003012.5:c.156C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.39

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 -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. 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 FAILED quality control check.
• BS2: High AC in GnomAd4 at 309 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFRP1	NM_003012.5	c.156C>T	p.Tyr52Tyr	synonymous_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.156C>T	p.Tyr52Tyr	synonymous_variant	Exon 1 of 3	1	NM_003012.5	ENSP00000220772.3

Frequencies

GnomAD3 genomes AF: 0.00200 AC: 304 AN: 152200 Hom.: 3 Cov.: 33

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

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.: 27 Cov.: 31 AF XY: 0.00115 AC XY: 833 AN XY: 726524

Gnomad4 AFR exome AF: 0.000239 AC: 8 AN: 33476

Gnomad4 AMR exome AF: 0.0289 AC: 1293 AN: 44714

Gnomad4 ASJ exome AF: 0.000153 AC: 4 AN: 26130

Gnomad4 EAS exome AF: 0.0106 AC: 419 AN: 39688

Gnomad4 SAS exome AF: 0.000719 AC: 62 AN: 86244

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 51834

Gnomad4 NFE exome AF: 0.0000306 AC: 34 AN: 1111900

Gnomad4 Remaining exome AF: 0.00103 AC: 62 AN: 60378

GnomAD4 genome AF: 0.00203 AC: 309 AN: 152318 Hom.: 3 Cov.: 33 AF XY: 0.00216 AC XY: 161 AN XY: 74468

Gnomad4 AFR AF: 0.000337 AC: 0.000336619 AN: 0.000336619

Gnomad4 AMR AF: 0.0155 AC: 0.0155434 AN: 0.0155434

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00777 AC: 0.00777001 AN: 0.00777001

Gnomad4 SAS AF: 0.00104 AC: 0.0010352 AN: 0.0010352

Gnomad4 FIN AF: 0.00 AC: 0 AN: 0

Gnomad4 NFE AF: 0.000103 AC: 0.000102905 AN: 0.000102905

Gnomad4 OTH AF: 0.00236 AC: 0.00236295 AN: 0.00236295

Alfa AF: 0.000690 Hom.: 1

Bravo AF: 0.00354

Asia WGS AF: 0.00577 AC: 20 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 06, 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	-0.58
CADD	Benign	13
DANN	Uncertain	0.97
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs184528079; hg19: chr8-41166523;