NM_001029871.4:c.79+11665T>C

Variant names:

• chr20-990421-A-G
• rs6056462
• NM_001029871.4:c.79+11665T>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+11665T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 151,948 control chromosomes in the GnomAD database, including 14,461 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 0.35 (14461 hom., cov: 32)
• Consequence: RSPO4 NM_001029871.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0150
• Publications: 2 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, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.749 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+11665T>C		intron	N/A	NP_001025042.2
	RSPO4	NM_001040007.3		c.79+11665T>C		intron	N/A	NP_001035096.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RSPO4	ENST00000217260.9	TSL:1 MANE Select	c.79+11665T>C		intron	N/A	ENSP00000217260.4
	RSPO4	ENST00000400634.2	TSL:1	c.79+11665T>C		intron	N/A	ENSP00000383475.2
	RSPO4	ENST00000873320.1		c.79+11665T>C		intron	N/A	ENSP00000543379.1

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53056 AN: 151830 Hom.: 14419 Cov.: 32

Gnomad AFR AF: 0.756

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.350 AC: 53154 AN: 151948 Hom.: 14461 Cov.: 32 AF XY: 0.345 AC XY: 25587 AN XY: 74264

African (AFR) AF: 0.756 AC: 31348 AN: 41454

American (AMR) AF: 0.257 AC: 3929 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1150 AN: 3470

East Asian (EAS) AF: 0.396 AC: 2045 AN: 5158

South Asian (SAS) AF: 0.239 AC: 1149 AN: 4802

European-Finnish (FIN) AF: 0.109 AC: 1155 AN: 10574

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.168 AC: 11420 AN: 67890

Other (OTH) AF: 0.356 AC: 753 AN: 2114

Alfa AF: 0.195 Hom.: 3366

Bravo AF: 0.381

Asia WGS AF: 0.355 AC: 1233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.3
DANN	Benign	0.51
PhyloP100		-0.015
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: rs6056462; hg19: chr20-971064;