rs2598116

Variant names:

• chr7-37906746-A-C
• rs2598116
• NM_003014.4:c.*733T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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=-0.82).
• 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 rank	MANE	Protein	UniProt
SFRP4	NM_003014.4	c.*733T>G		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.*733T>G		3_prime_UTR_variant	Exon 6 of 6	1	NM_003014.4	ENSP00000410715.2
ENSG00000290149	ENST00000476620.1	c.-37-42094A>C		intron_variant	Intron 2 of 3	4		ENSP00000425858.1

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

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

African (AFR) AF: 0.119 AC: 4956 AN: 41500

American (AMR) AF: 0.114 AC: 1743 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 628 AN: 3470

East Asian (EAS) AF: 0.225 AC: 1167 AN: 5186

South Asian (SAS) AF: 0.235 AC: 1132 AN: 4820

European-Finnish (FIN) AF: 0.101 AC: 1076 AN: 10606

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.135 AC: 9207 AN: 68010

Other (OTH) AF: 0.139 AC: 293 AN: 2114

Alfa AF: 0.134 Hom.: 2660

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
PhyloP100		0.61
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: rs2598116; hg19: chr7-37946348;