rs6140882

Variant names:

• chr20-987314-A-G
• rs6140882
• NM_001029871.4:c.79+14772T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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]

RSPO4 Gene-Disease associations (from GenCC):

• nonsyndromic congenital nail disorder 4

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, G2P, PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001029871.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSPO4	NM_001029871.4	MANE Select	c.79+14772T>C		intron	N/A	NP_001025042.2	Q2I0M5-1
	RSPO4	NM_001040007.3		c.79+14772T>C		intron	N/A	NP_001035096.1	Q2I0M5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSPO4	ENST00000217260.9	TSL:1 MANE Select	c.79+14772T>C		intron	N/A	ENSP00000217260.4	Q2I0M5-1
	RSPO4	ENST00000400634.2	TSL:1	c.79+14772T>C		intron	N/A	ENSP00000383475.2	Q2I0M5-2
	RSPO4	ENST00000873320.1		c.79+14772T>C		intron	N/A	ENSP00000543379.1

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

African (AFR) AF: 0.767 AC: 31791 AN: 41432

American (AMR) AF: 0.253 AC: 3862 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 945 AN: 3468

East Asian (EAS) AF: 0.393 AC: 2030 AN: 5160

South Asian (SAS) AF: 0.236 AC: 1135 AN: 4818

European-Finnish (FIN) AF: 0.0969 AC: 1027 AN: 10604

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10526 AN: 67974

Other (OTH) AF: 0.350 AC: 738 AN: 2108

Alfa AF: 0.248 Hom.: 11900

Bravo AF: 0.376

Asia WGS AF: 0.344 AC: 1194 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.12
DANN	Benign	0.42
PhyloP100		-1.8
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: rs6140882; hg19: chr20-967957;