rs2598116

Positions:

• chr7-37906746-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003014.4(SFRP4):​c.*733T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,192 control chromosomes in the GnomAD database, including 1,479 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 0.13 (1479 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: SFRP4 NM_003014.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.612

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SFRP4	NM_003014.4	c.*733T>G		3_prime_UTR_variant	6/6	ENST00000436072.7	NP_003005.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SFRP4	ENST00000436072.7	c.*733T>G		3_prime_UTR_variant	6/6	1	NM_003014.4	ENSP00000410715	P1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20369 AN: 152074 Hom.: 1474 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.134 AC: 20378 AN: 152192 Hom.: 1479 Cov.: 32 AF XY: 0.133 AC XY: 9904 AN XY: 74404

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.235

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.135

Gnomad4 OTH AF: 0.139

Alfa AF: 0.136 Hom.: 1981

Bravo AF: 0.131

Asia WGS AF: 0.206 AC: 718 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.99
DANN	Benign	0.79

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: rs2598116; hg19: chr7-37946348;