chr1-37612958-A-T

Position:

• chr1-37612958-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001242908.2(RSPO1):​c.626-37T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 1,611,032 control chromosomes in the GnomAD database, including 52,591 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.21 (3843 hom., cov: 33)
  • Exomes 𝑓: 0.26 (48748 hom.)
• Consequence: RSPO1 NM_001242908.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.18

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-37612958-A-T is Benign according to our data. Variant chr1-37612958-A-T is described in ClinVar as [Benign]. Clinvar id is 1229324.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RSPO1	NM_001242908.2	c.626-37T>A		intron_variant		ENST00000356545.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSPO1	ENST00000356545.7	c.626-37T>A		intron_variant		1	NM_001242908.2	P1
RSPO1	ENST00000401068.1	c.626-37T>A		intron_variant		1		P1
RSPO1	ENST00000612451.4	c.437-37T>A		intron_variant		1
RSPO1	ENST00000615459.4	c.545-37T>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31972 AN: 152080 Hom.: 3845 Cov.: 33

Gnomad AFR AF: 0.0949

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.235

GnomAD3 exomes AF: 0.246 AC: 60690 AN: 246774 Hom.: 7825 AF XY: 0.247 AC XY: 33159 AN XY: 134040

Gnomad AFR exome AF: 0.0892

Gnomad AMR exome AF: 0.243

Gnomad ASJ exome AF: 0.331

Gnomad EAS exome AF: 0.322

Gnomad SAS exome AF: 0.238

Gnomad FIN exome AF: 0.196

Gnomad NFE exome AF: 0.259

Gnomad OTH exome AF: 0.266

GnomAD4 exome AF: 0.256 AC: 373190 AN: 1458834 Hom.: 48748 Cov.: 33 AF XY: 0.256 AC XY: 185911 AN XY: 725860

Gnomad4 AFR exome AF: 0.0846

Gnomad4 AMR exome AF: 0.242

Gnomad4 ASJ exome AF: 0.331

Gnomad4 EAS exome AF: 0.272

Gnomad4 SAS exome AF: 0.242

Gnomad4 FIN exome AF: 0.195

Gnomad4 NFE exome AF: 0.263

Gnomad4 OTH exome AF: 0.257

GnomAD4 genome AF: 0.210 AC: 31952 AN: 152198 Hom.: 3843 Cov.: 33 AF XY: 0.209 AC XY: 15526 AN XY: 74418

Gnomad4 AFR AF: 0.0946

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.329

Gnomad4 EAS AF: 0.288

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.233

Alfa AF: 0.247 Hom.: 930

Bravo AF: 0.212

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.1
DANN	Benign	0.73

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: rs55852308; hg19: chr1-38078630; COSMIC: COSV62974389;