chr1-37627051-C-T

Position:

• chr1-37627051-C-T

Variant summary

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

The NM_001242908.2(RSPO1):​c.94+2517G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 151,998 control chromosomes in the GnomAD database, including 12,683 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 0.39 (12683 hom., cov: 30)
• Consequence: RSPO1 NM_001242908.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.460

Genes affected

RSPO1 (HGNC:21679): (R-spondin 1) This gene encodes a secreted activator protein with two cysteine-rich, furin-like domains and one thrombospondin type 1 domain. The encoded protein is a ligand for leucine-rich repeat-containing G-protein coupled receptors (LGR proteins) and positively regulates the Wnt signaling pathway. In mice, the protein induces the rapid onset of crypt cell proliferation and increases intestinal epithelial healing, providing a protective effect against chemotherapy-induced adverse effects. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSPO1	NM_001242908.2	c.94+2517G>A		intron_variant		ENST00000356545.7	NP_001229837.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSPO1	ENST00000356545.7	c.94+2517G>A		intron_variant		1	NM_001242908.2	ENSP00000348944.2
RSPO1	ENST00000401068.1	c.94+2517G>A		intron_variant		1		ENSP00000383846.1
RSPO1	ENST00000612451.4	c.94+2517G>A		intron_variant		1		ENSP00000479832.1
RSPO1	ENST00000615459.4	c.13+2838G>A		intron_variant		2		ENSP00000481178.1

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59653 AN: 151880 Hom.: 12666 Cov.: 30

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.419

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

GnomAD4 genome AF: 0.393 AC: 59703 AN: 151998 Hom.: 12683 Cov.: 30 AF XY: 0.397 AC XY: 29500 AN XY: 74264

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.510

Gnomad4 SAS AF: 0.413

Gnomad4 FIN AF: 0.515

Gnomad4 NFE AF: 0.439

Gnomad4 OTH AF: 0.423

Alfa AF: 0.429 Hom.: 29138

Bravo AF: 0.383

Asia WGS AF: 0.488 AC: 1696 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	7.0
DANN	Benign	0.89

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: rs4074961; hg19: chr1-38092723; COSMIC: COSV62974990;