rs2503107

Variant names:

• chr6-127142231-C-A
• rs2503107
• NM_032784.5:c.98-6417C>A

Variant summary

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

The NM_032784.5(RSPO3):​c.98-6417C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 151,930 control chromosomes in the GnomAD database, including 23,804 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 0.56 (23804 hom., cov: 32)
• Consequence: RSPO3 NM_032784.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.102
• Publications: 9 publications found

Genes affected

RSPO3 (HGNC:20866): (R-spondin 3) This gene belongs to the R-spondin family. The encoded protein plays a role in the regulation of Wnt (wingless-type MMTV integration site family)/beta-catenin and Wnt/planar cell polarity (PCP) signaling pathways, which are involved in development, cell growth and disease pathogenesis. Genome-wide association studies suggest a correlation of this gene with bone mineral density and risk of fracture. This gene may be involved in tumor development. [provided by RefSeq, Jul 2013]

ENSG00000293110 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RSPO3	NM_032784.5	c.98-6417C>A		intron_variant	Intron 1 of 4	ENST00000356698.9	NP_116173.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RSPO3	ENST00000356698.9	c.98-6417C>A		intron_variant	Intron 1 of 4	1	NM_032784.5	ENSP00000349131.4

Frequencies

GnomAD3 genomes AF: 0.560 AC: 84942 AN: 151816 Hom.: 23772 Cov.: 32

Gnomad AFR AF: 0.601

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.545

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

GnomAD4 genome AF: 0.560 AC: 85035 AN: 151930 Hom.: 23804 Cov.: 32 AF XY: 0.557 AC XY: 41331 AN XY: 74248

African (AFR) AF: 0.601 AC: 24913 AN: 41440

American (AMR) AF: 0.554 AC: 8438 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1596 AN: 3466

East Asian (EAS) AF: 0.585 AC: 3026 AN: 5176

South Asian (SAS) AF: 0.536 AC: 2579 AN: 4816

European-Finnish (FIN) AF: 0.539 AC: 5689 AN: 10552

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.545 AC: 37004 AN: 67936

Other (OTH) AF: 0.551 AC: 1160 AN: 2106

Alfa AF: 0.564 Hom.: 7078

Bravo AF: 0.566

Asia WGS AF: 0.583 AC: 2028 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.1
DANN	Benign	0.61
PhyloP100		-0.10
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: rs2503107; hg19: chr6-127463376;