rs6569474

Positions:

• chr6-127172466-A-T

Variant summary

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

The ENST00000356698.9(RSPO3):​c.634+17028A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 151,304 control chromosomes in the GnomAD database, including 21,649 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 0.53 (21649 hom., cov: 31)
• Consequence: RSPO3 ENST00000356698.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.121

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=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSPO3	NM_032784.5	c.634+17028A>T		intron_variant		ENST00000356698.9	NP_116173.2
LOC105377989	XR_002956387.2	n.489+4850T>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSPO3	ENST00000356698.9	c.634+17028A>T		intron_variant		1	NM_032784.5	ENSP00000349131	P1

Frequencies

GnomAD3 genomes AF: 0.534 AC: 80808 AN: 151188 Hom.: 21628 Cov.: 31

Gnomad AFR AF: 0.567

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.504

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

GnomAD4 genome AF: 0.535 AC: 80878 AN: 151304 Hom.: 21649 Cov.: 31 AF XY: 0.530 AC XY: 39187 AN XY: 73908

Gnomad4 AFR AF: 0.567

Gnomad4 AMR AF: 0.479

Gnomad4 ASJ AF: 0.463

Gnomad4 EAS AF: 0.530

Gnomad4 SAS AF: 0.535

Gnomad4 FIN AF: 0.496

Gnomad4 NFE AF: 0.539

Gnomad4 OTH AF: 0.510

Alfa AF: 0.538 Hom.: 12191

Bravo AF: 0.535

Asia WGS AF: 0.541 AC: 1882 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	12
DANN	Benign	0.89

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: rs6569474; hg19: chr6-127493611;