rs1052981

Variant names:

• chr7-37906899-G-A
• rs1052981
• NM_003014.4:c.*580C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003014.4(SFRP4):​c.*580C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.702 in 152,070 control chromosomes in the GnomAD database, including 37,853 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.70 (37853 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: SFRP4 NM_003014.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.178
• Publications: 17 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000290149 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SFRP4	NM_003014.4	c.*580C>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000436072.7	NP_003005.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SFRP4	ENST00000436072.7	c.*580C>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_003014.4	ENSP00000410715.2
ENSG00000290149	ENST00000476620.1	c.-37-41941G>A		intron_variant	Intron 2 of 3	4		ENSP00000425858.1

Frequencies

GnomAD3 genomes AF: 0.703 AC: 106750 AN: 151952 Hom.: 37833 Cov.: 31

Gnomad AFR AF: 0.616

Gnomad AMI AF: 0.791

Gnomad AMR AF: 0.634

Gnomad ASJ AF: 0.770

Gnomad EAS AF: 0.771

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.743

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.756

Gnomad OTH AF: 0.720

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.702 AC: 106807 AN: 152070 Hom.: 37853 Cov.: 31 AF XY: 0.699 AC XY: 52003 AN XY: 74358

African (AFR) AF: 0.616 AC: 25523 AN: 41438

American (AMR) AF: 0.633 AC: 9682 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.770 AC: 2674 AN: 3472

East Asian (EAS) AF: 0.771 AC: 3991 AN: 5178

South Asian (SAS) AF: 0.679 AC: 3272 AN: 4820

European-Finnish (FIN) AF: 0.743 AC: 7860 AN: 10576

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.756 AC: 51379 AN: 67982

Other (OTH) AF: 0.715 AC: 1511 AN: 2112

Alfa AF: 0.736 Hom.: 41791

Bravo AF: 0.694

Asia WGS AF: 0.690 AC: 2396 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.44
DANN	Benign	0.48
PhyloP100		-0.18
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: rs1052981; hg19: chr7-37946501;