Variant chr1-37612958-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.18

Variant links:

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]

RSPO1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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	Protein	UniProt
RSPO1	NM_001242908.2 linkuse as main transcript	c.626-37T>A		intron_variant		ENST00000356545.7	NP_001229837.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
RSPO1	ENST00000356545.7 linkuse as main transcript	c.626-37T>A	intron_variant	1	NM_001242908.2	ENSP00000348944	P1	Q2MKA7-1
RSPO1	ENST00000401068.1 linkuse as main transcript	c.626-37T>A	intron_variant	1		ENSP00000383846	P1	Q2MKA7-1
RSPO1	ENST00000612451.4 linkuse as main transcript	c.437-37T>A	intron_variant	1		ENSP00000479832		Q2MKA7-3
RSPO1	ENST00000615459.4 linkuse as main transcript	c.545-37T>A	intron_variant	2		ENSP00000481178		Q2MKA7-2

Frequencies

GnomAD3 genomes

AF:

0.210

AC:

31972

AN:

152080

Hom.:

3845

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.256

AC XY:

185911

AN XY:

725860

show subpopulations

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.:

AF XY:

0.209

AC XY:

15526

AN XY:

74418

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over