rs1376264

Variant names:

• chr7-37918687-G-A
• rs1376264
• ENST00000476620.1:c.-37-30153G>A

Variant summary

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

The ENST00000476620.1(ENSG00000290149):​c.-37-30153G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 151,972 control chromosomes in the GnomAD database, including 5,043 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 0.25 (5043 hom., cov: 32)
• Consequence: ENSG00000290149 ENST00000476620.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135

Genes affected

ENSG00000290149 (HGNC:):

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000290149	ENST00000476620.1	c.-37-30153G>A		intron_variant	Intron 2 of 3	4		ENSP00000425858.1
SFRP4	ENST00000447200.2	c.44-4234C>T		intron_variant	Intron 2 of 5	5		ENSP00000402262.2

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37368 AN: 151854 Hom.: 5037 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.239

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.246 AC: 37384 AN: 151972 Hom.: 5043 Cov.: 32 AF XY: 0.244 AC XY: 18128 AN XY: 74274

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.325

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.244

Alfa AF: 0.298 Hom.: 14167

Bravo AF: 0.233

Asia WGS AF: 0.185 AC: 644 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.88
DANN	Benign	0.71

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1376264; hg19: chr7-37958289;