20-990421-A-G

Position:

• chr20-990421-A-G

Variant summary

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

The ENST00000217260.9(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 ENST00000217260.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0150

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSPO4	NM_001029871.4	c.79+11665T>C		intron_variant		ENST00000217260.9	NP_001025042.2
RSPO4	NM_001040007.3	c.79+11665T>C		intron_variant			NP_001035096.1
RSPO4	XM_017027839.2	c.79+11665T>C		intron_variant			XP_016883328.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSPO4	ENST00000217260.9	c.79+11665T>C		intron_variant		1	NM_001029871.4	ENSP00000217260	P1
RSPO4	ENST00000400634.2	c.79+11665T>C		intron_variant		1		ENSP00000383475

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

Gnomad4 AFR AF: 0.756

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.331

Gnomad4 EAS AF: 0.396

Gnomad4 SAS AF: 0.239

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.356

Alfa AF: 0.192 Hom.: 2649

Bravo AF: 0.381

Asia WGS AF: 0.355 AC: 1233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.3
DANN	Benign	0.51

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: rs6056462; hg19: chr20-971064;