rs1132552

Variant names:

• chr7-37914238-C-T
• rs1132552
• NM_003014.4:c.567G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-37914238-C-T
• chr7-37914238-C-G

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.567G>A​(p.Thr189Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 1,612,808 control chromosomes in the GnomAD database, including 151,674 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.45 (15387 hom., cov: 33)
  • Exomes 𝑓: 0.43 (136287 hom.)
• Consequence: SFRP4 NM_003014.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -4.97
• Publications: 26 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=-0.65).
• BP6: Variant 7-37914238-C-T is Benign according to our data. Variant chr7-37914238-C-T is described in ClinVar as Benign. ClinVar VariationId is 1332948.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.97 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.621 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.567G>A	p.Thr189Thr	synonymous	Exon 3 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.567G>A	p.Thr189Thr	synonymous	Exon 3 of 6	ENSP00000410715.2	Q6FHJ7
	ENSG00000290149	ENST00000476620.1	TSL:4	c.-37-34602C>T		intron	N/A	ENSP00000425858.1	D6RIH7
	SFRP4	ENST00000960684.1		c.567G>A	p.Thr189Thr	synonymous	Exon 3 of 6	ENSP00000630743.1

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67626 AN: 151898 Hom.: 15364 Cov.: 33

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.639

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.434

GnomAD2 exomes AF: 0.460 AC: 115715 AN: 251382 AF XY: 0.463

Gnomad AFR exome AF: 0.481

Gnomad AMR exome AF: 0.468

Gnomad ASJ exome AF: 0.426

Gnomad EAS exome AF: 0.636

Gnomad FIN exome AF: 0.422

Gnomad NFE exome AF: 0.403

Gnomad OTH exome AF: 0.434

GnomAD4 exome AF: 0.428 AC: 625023 AN: 1460792 Hom.: 136287 Cov.: 37 AF XY: 0.432 AC XY: 313782 AN XY: 726760

African (AFR) AF: 0.479 AC: 16021 AN: 33458

American (AMR) AF: 0.469 AC: 20985 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 11163 AN: 26120

East Asian (EAS) AF: 0.618 AC: 24541 AN: 39694

South Asian (SAS) AF: 0.587 AC: 50606 AN: 86224

European-Finnish (FIN) AF: 0.423 AC: 22585 AN: 53416

Middle Eastern (MID) AF: 0.479 AC: 2761 AN: 5768

European-Non Finnish (NFE) AF: 0.405 AC: 450291 AN: 1111046

Other (OTH) AF: 0.432 AC: 26070 AN: 60364

GnomAD4 genome AF: 0.445 AC: 67686 AN: 152016 Hom.: 15387 Cov.: 33 AF XY: 0.451 AC XY: 33555 AN XY: 74322

African (AFR) AF: 0.472 AC: 19557 AN: 41424

American (AMR) AF: 0.482 AC: 7367 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1456 AN: 3472

East Asian (EAS) AF: 0.639 AC: 3302 AN: 5164

South Asian (SAS) AF: 0.595 AC: 2869 AN: 4820

European-Finnish (FIN) AF: 0.433 AC: 4575 AN: 10568

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.400 AC: 27166 AN: 67976

Other (OTH) AF: 0.439 AC: 924 AN: 2106

Alfa AF: 0.414 Hom.: 41172

Bravo AF: 0.442

Asia WGS AF: 0.592 AC: 2058 AN: 3478

EpiCase AF: 0.405

EpiControl AF: 0.406

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	-0.65
CADD	Benign	0.61
DANN	Benign	0.84
PhyloP100		-5.0
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: rs1132552; hg19: chr7-37953840; COSMIC: COSV71412406; COSMIC: COSV71412406;