chr6-127188012-G-A

Variant names:

• chr6-127188012-G-A
• rs7745274
• NM_032784.5:c.635-7811G>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.635-7811G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 151,828 control chromosomes in the GnomAD database, including 23,930 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 (23930 hom., cov: 32)
• Consequence: RSPO3 NM_032784.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.669
• Publications: 26 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032784.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSPO3	NM_032784.5	MANE Select	c.635-7811G>A		intron	N/A	NP_116173.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSPO3	ENST00000356698.9	TSL:1 MANE Select	c.635-7811G>A		intron	N/A	ENSP00000349131.4
	RSPO3	ENST00000368317.3	TSL:2	c.635-7811G>A		intron	N/A	ENSP00000357300.3
	ENSG00000293110	ENST00000650648.1		n.25-8016C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85070 AN: 151708 Hom.: 23899 Cov.: 32

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.536

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.585

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.545

Gnomad OTH AF: 0.542

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

GnomAD4 genome AF: 0.561 AC: 85162 AN: 151828 Hom.: 23930 Cov.: 32 AF XY: 0.558 AC XY: 41387 AN XY: 74220

African (AFR) AF: 0.608 AC: 25142 AN: 41348

American (AMR) AF: 0.546 AC: 8327 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 1640 AN: 3464

East Asian (EAS) AF: 0.585 AC: 3005 AN: 5138

South Asian (SAS) AF: 0.539 AC: 2598 AN: 4820

European-Finnish (FIN) AF: 0.534 AC: 5621 AN: 10530

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.545 AC: 37037 AN: 67952

Other (OTH) AF: 0.548 AC: 1159 AN: 2114

Alfa AF: 0.549 Hom.: 56529

Bravo AF: 0.569

Asia WGS AF: 0.582 AC: 2022 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.088
DANN	Benign	0.21
PhyloP100		-0.67
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: rs7745274; hg19: chr6-127509157; COSMIC: COSV63150396;