rs6140882

Positions:

• chr20-987314-A-G

Variant summary

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

The NM_001029871.4(RSPO4):​c.79+14772T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 152,054 control chromosomes in the GnomAD database, including 14,575 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 0.34 (14575 hom., cov: 32)
• Consequence: RSPO4 NM_001029871.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78

Genes affected

RSPO4 (HGNC:16175): (R-spondin 4) This gene encodes a member of the R-spondin family of proteins that share a common domain organization consisting of a signal peptide, cysteine-rich/furin-like domain, thrombospondin domain and a C-terminal basic region. The encoded protein may be involved in activation of Wnt/beta-catenin signaling pathways. Mutations in this gene are associated with anonychia congenital. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSPO4	NM_001029871.4	c.79+14772T>C		intron_variant		ENST00000217260.9	NP_001025042.2
RSPO4	NM_001040007.3	c.79+14772T>C		intron_variant			NP_001035096.1
RSPO4	XM_017027839.2	c.79+14772T>C		intron_variant			XP_016883328.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSPO4	ENST00000217260.9	c.79+14772T>C		intron_variant		1	NM_001029871.4	ENSP00000217260	P1
RSPO4	ENST00000400634.2	c.79+14772T>C		intron_variant		1		ENSP00000383475

Frequencies

GnomAD3 genomes AF: 0.343 AC: 52134 AN: 151936 Hom.: 14529 Cov.: 32

Gnomad AFR AF: 0.767

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.0969

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.344 AC: 52241 AN: 152054 Hom.: 14575 Cov.: 32 AF XY: 0.338 AC XY: 25085 AN XY: 74324

Gnomad4 AFR AF: 0.767

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.0969

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.350

Alfa AF: 0.265 Hom.: 1434

Bravo AF: 0.376

Asia WGS AF: 0.344 AC: 1194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.12
DANN	Benign	0.42

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: rs6140882; hg19: chr20-967957;