rs7741021

Positions:

• chr6-127147129-A-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000356698.9(RSPO3):​c.98-1519A>C variant causes a intron change. The variant allele was found at a frequency of 0.416 in 151,862 control chromosomes in the GnomAD database, including 13,511 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 0.42 (13511 hom., cov: 31)
• Consequence: RSPO3 ENST00000356698.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.44

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSPO3	NM_032784.5	c.98-1519A>C		intron_variant		ENST00000356698.9	NP_116173.2
LOC105377989	XR_002956387.2	n.490-25393T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSPO3	ENST00000356698.9	c.98-1519A>C		intron_variant		1	NM_032784.5	ENSP00000349131	P1

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63208 AN: 151744 Hom.: 13509 Cov.: 31

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.279

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.394

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

GnomAD4 genome AF: 0.416 AC: 63225 AN: 151862 Hom.: 13511 Cov.: 31 AF XY: 0.415 AC XY: 30818 AN XY: 74180

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.412

Gnomad4 ASJ AF: 0.346

Gnomad4 EAS AF: 0.510

Gnomad4 SAS AF: 0.420

Gnomad4 FIN AF: 0.455

Gnomad4 NFE AF: 0.472

Gnomad4 OTH AF: 0.400

Alfa AF: 0.445 Hom.: 1883

Bravo AF: 0.409

Asia WGS AF: 0.454 AC: 1579 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	18
DANN	Benign	0.79

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: rs7741021; hg19: chr6-127468274; COSMIC: COSV63150251;