rs2503322

chr6-127136115-A-Gchr6-127136115-A-T

Variant summary

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

The NM_032784.5(RSPO3):c.98-12533A>G 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 151,850 control chromosomes in the GnomAD database, including 23,842 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 (23842 hom., cov: 30)
• Consequence: RSPO3 NM_032784.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990

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]

LOC105377989 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• 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/exons	MANE	UniProt
RSPO3	NM_032784.5	c.98-12533A>G		intron_variant		ENST00000356698.9
LOC105377989	XR_002956387.2	n.490-14379T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSPO3	ENST00000356698.9	c.98-12533A>G		intron_variant		1	NM_032784.5	P1

Frequencies

GnomAD3 genomes AF: 0.560 AC: 85006 AN: 151730 Hom.: 23812 Cov.: 30

Gnomad AFR AF: 0.601

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.593

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.540

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.560 AC: 85097 AN: 151850 Hom.: 23842 Cov.: 30 AF XY: 0.558 AC XY: 41389 AN XY: 74232

Gnomad4 AFR AF: 0.602

Gnomad4 AMR AF: 0.553

Gnomad4 ASJ AF: 0.459

Gnomad4 EAS AF: 0.593

Gnomad4 SAS AF: 0.537

Gnomad4 FIN AF: 0.540

Gnomad4 NFE AF: 0.545

Gnomad4 OTH AF: 0.553

Alfa AF: 0.550 Hom.: 11611

Bravo AF: 0.567

Asia WGS AF: 0.585 AC: 2036 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	1.6
Dann	Benign	0.70

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: rs2503322; hg19: chr6-127457260; COSMIC: COSV63150196;