chr6-127131494-C-G

Position:

• chr6-127131494-C-G

Variant summary

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

The ENST00000356698.9(RSPO3):​c.97+12205C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 151,856 control chromosomes in the GnomAD database, including 15,488 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 0.45 (15488 hom., cov: 32)
• Consequence: RSPO3 ENST00000356698.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.734

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSPO3	NM_032784.5	c.97+12205C>G		intron_variant		ENST00000356698.9	NP_116173.2
LOC105377989	XR_002956387.2	n.490-9758G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSPO3	ENST00000356698.9	c.97+12205C>G		intron_variant		1	NM_032784.5	ENSP00000349131	P1

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68459 AN: 151738 Hom.: 15483 Cov.: 32

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.451 AC: 68490 AN: 151856 Hom.: 15488 Cov.: 32 AF XY: 0.450 AC XY: 33396 AN XY: 74250

Gnomad4 AFR AF: 0.387

Gnomad4 AMR AF: 0.449

Gnomad4 ASJ AF: 0.387

Gnomad4 EAS AF: 0.529

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.456

Gnomad4 NFE AF: 0.487

Gnomad4 OTH AF: 0.439

Alfa AF: 0.477 Hom.: 9519

Bravo AF: 0.448

Asia WGS AF: 0.491 AC: 1707 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.0
DANN	Benign	0.64

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: rs9491696; hg19: chr6-127452639;