NM_003014.4:c.786C>T

Variant names:

• chr7-37912124-G-A
• rs1132553
• NM_003014.4:c.786C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_003014.4(SFRP4):​c.786C>T​(p.Arg262Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 1,611,562 control chromosomes in the GnomAD database, including 262,640 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.54 (22554 hom., cov: 32)
  • Exomes 𝑓: 0.57 (240086 hom.)
• Consequence: SFRP4 NM_003014.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.268
• Publications: 27 publications found

Genes affected

SFRP4 (HGNC:10778): (secreted frizzled related protein 4) Secreted frizzled-related protein 4 (SFRP4) is 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. The expression of SFRP4 in ventricular myocardium correlates with apoptosis related gene expression. [provided by RefSeq, Jul 2008]

SFRP4 Gene-Disease associations (from GenCC):

• Pyle disease

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000290149 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 7-37912124-G-A is Benign according to our data. Variant chr7-37912124-G-A is described in ClinVar as Benign. ClinVar VariationId is 1332947.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.268 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003014.4. 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
	SFRP4	NM_003014.4	MANE Select	c.786C>T	p.Arg262Arg	synonymous	Exon 4 of 6	NP_003005.2	Q6FHJ7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SFRP4	ENST00000436072.7	TSL:1 MANE Select	c.786C>T	p.Arg262Arg	synonymous	Exon 4 of 6	ENSP00000410715.2	Q6FHJ7
	ENSG00000290149	ENST00000476620.1	TSL:4	c.-37-36716G>A		intron	N/A	ENSP00000425858.1	D6RIH7
	SFRP4	ENST00000960684.1		c.786C>T	p.Arg262Arg	synonymous	Exon 4 of 6	ENSP00000630743.1

Frequencies

GnomAD3 genomes AF: 0.540 AC: 82006 AN: 151834 Hom.: 22535 Cov.: 32

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.580

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.397

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.549

GnomAD2 exomes AF: 0.535 AC: 134352 AN: 251252 AF XY: 0.533

Gnomad AFR exome AF: 0.468

Gnomad AMR exome AF: 0.528

Gnomad ASJ exome AF: 0.572

Gnomad EAS exome AF: 0.363

Gnomad FIN exome AF: 0.578

Gnomad NFE exome AF: 0.596

Gnomad OTH exome AF: 0.563

GnomAD4 exome AF: 0.570 AC: 832199 AN: 1459610 Hom.: 240086 Cov.: 34 AF XY: 0.566 AC XY: 411254 AN XY: 726188

African (AFR) AF: 0.471 AC: 15752 AN: 33416

American (AMR) AF: 0.527 AC: 23546 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 14909 AN: 26112

East Asian (EAS) AF: 0.382 AC: 15153 AN: 39690

South Asian (SAS) AF: 0.408 AC: 35119 AN: 86174

European-Finnish (FIN) AF: 0.577 AC: 30826 AN: 53406

Middle Eastern (MID) AF: 0.516 AC: 2976 AN: 5764

European-Non Finnish (NFE) AF: 0.595 AC: 659909 AN: 1110016

Other (OTH) AF: 0.564 AC: 34009 AN: 60314

GnomAD4 genome AF: 0.540 AC: 82057 AN: 151952 Hom.: 22554 Cov.: 32 AF XY: 0.533 AC XY: 39620 AN XY: 74266

African (AFR) AF: 0.478 AC: 19786 AN: 41412

American (AMR) AF: 0.511 AC: 7805 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 2011 AN: 3468

East Asian (EAS) AF: 0.361 AC: 1866 AN: 5162

South Asian (SAS) AF: 0.397 AC: 1910 AN: 4806

European-Finnish (FIN) AF: 0.569 AC: 5995 AN: 10544

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.600 AC: 40807 AN: 67978

Other (OTH) AF: 0.545 AC: 1150 AN: 2112

Alfa AF: 0.581 Hom.: 100987

Bravo AF: 0.541

Asia WGS AF: 0.400 AC: 1390 AN: 3478

EpiCase AF: 0.594

EpiControl AF: 0.593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Pyle metaphyseal dysplasia (1)
-	-	1	SFRP4-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	5.8
DANN	Benign	0.79
PhyloP100		0.27
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1132553; hg19: chr7-37951726; COSMIC: COSV71412396; COSMIC: COSV71412396;