rs7741021

Variant names:

• chr6-127147129-A-C
• rs7741021
• NM_032784.5:c.98-1519A>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_032784.5(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 NM_032784.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.44
• Publications: 27 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 -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 rank	MANE	Protein	UniProt
RSPO3	NM_032784.5	c.98-1519A>C		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.98-1519A>C		intron_variant	Intron 1 of 4	1	NM_032784.5	ENSP00000349131.4

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

African (AFR) AF: 0.311 AC: 12878 AN: 41418

American (AMR) AF: 0.412 AC: 6275 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1199 AN: 3464

East Asian (EAS) AF: 0.510 AC: 2614 AN: 5128

South Asian (SAS) AF: 0.420 AC: 2021 AN: 4808

European-Finnish (FIN) AF: 0.455 AC: 4794 AN: 10546

Middle Eastern (MID) AF: 0.272 AC: 79 AN: 290

European-Non Finnish (NFE) AF: 0.472 AC: 32090 AN: 67948

Other (OTH) AF: 0.400 AC: 844 AN: 2112

Alfa AF: 0.444 Hom.: 4387

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
PhyloP100		5.4
Mutation Taster		=94/6	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: rs7741021; hg19: chr6-127468274; COSMIC: COSV63150251;