Variant chr1-37613845-T-G 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.484A>C(p.Lys162Gln) variant causes a missense change. The variant allele was found at a frequency of 0.056 in 1,613,898 control chromosomes in the GnomAD database, including 3,082 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.040 ( 178 hom., cov: 32)

Exomes 𝑓: 0.058 ( 2904 hom. )

Consequence

RSPO1
NM_001242908.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 5.63

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 (MetaRNN=0.0024950802).

BP6

Variant 1-37613845-T-G is Benign according to our data. Variant chr1-37613845-T-G is described in ClinVar as [Benign]. Clinvar id is 1616289.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.119 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.484A>C	p.Lys162Gln	missense_variant	6/7	ENST00000356545.7	NP_001229837.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSPO1	ENST00000356545.7 linkuse as main transcript	c.484A>C	p.Lys162Gln	missense_variant	6/7	1	NM_001242908.2	ENSP00000348944	P1	Q2MKA7-1
RSPO1	ENST00000401068.1 linkuse as main transcript	c.484A>C	p.Lys162Gln	missense_variant	7/8	1		ENSP00000383846	P1	Q2MKA7-1
RSPO1	ENST00000612451.4 linkuse as main transcript	c.436+339A>C		intron_variant		1		ENSP00000479832		Q2MKA7-3
RSPO1	ENST00000615459.4 linkuse as main transcript	c.403A>C	p.Lys135Gln	missense_variant	6/7	2		ENSP00000481178		Q2MKA7-2

Frequencies

GnomAD3 genomes

AF:

0.0404

AC:

6148

AN:

152146

Hom.:

178

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00989

Gnomad AMI

AF:

0.0899

Gnomad AMR

AF:

0.0330

Gnomad ASJ

AF:

0.0597

Gnomad EAS

AF:

0.0444

Gnomad SAS

AF:

0.127

Gnomad FIN

AF:

0.0291

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0543

Gnomad OTH

AF:

0.0421

GnomAD3 exomes

AF:

0.0516

AC:

12856

AN:

249324

Hom.:

503

AF XY:

0.0571

AC XY:

7728

AN XY:

135306

show subpopulations

Gnomad AFR exome

AF:

0.00924

Gnomad AMR exome

AF:

0.0198

Gnomad ASJ exome

AF:

0.0646

Gnomad EAS exome

AF:

0.0275

Gnomad SAS exome

AF:

0.128

Gnomad FIN exome

AF:

0.0284

Gnomad NFE exome

AF:

0.0534

Gnomad OTH exome

AF:

0.0504

GnomAD4 exome

AF:

0.0576

AC:

84221

AN:

1461634

Hom.:

2904

Cov.:

AF XY:

0.0601

AC XY:

43696

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.00854

Gnomad4 AMR exome

AF:

0.0210

Gnomad4 ASJ exome

AF:

0.0588

Gnomad4 EAS exome

AF:

0.0683

Gnomad4 SAS exome

AF:

0.127

Gnomad4 FIN exome

AF:

0.0277

Gnomad4 NFE exome

AF:

0.0563

Gnomad4 OTH exome

AF:

0.0540

GnomAD4 genome

AF:

0.0404

AC:

6150

AN:

152264

Hom.:

178

Cov.:

AF XY:

0.0409

AC XY:

3046

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00986

Gnomad4 AMR

AF:

0.0329

Gnomad4 ASJ

AF:

0.0597

Gnomad4 EAS

AF:

0.0443

Gnomad4 SAS

AF:

0.127

Gnomad4 FIN

AF:

0.0291

Gnomad4 NFE

AF:

0.0543

Gnomad4 OTH

AF:

0.0431

Alfa

AF:

0.0462

Hom.:

101

Bravo

AF:

0.0353

TwinsUK

AF:

0.0577

AC:

214

ALSPAC

AF:

0.0615

AC:

237

ESP6500AA

AF:

0.0115

AC:

ESP6500EA

AF:

0.0567

AC:

470

ExAC

AF:

0.0533

AC:

6440

Asia WGS

AF:

0.0990

AC:

344

AN:

3478

EpiCase

AF:

0.0594

EpiControl

AF:

0.0568

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 26, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

.;T;T

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.85

T;.;T

MetaRNN

Benign

0.0025

T;T;T

MetaSVM

Benign

-0.40

MutationAssessor

Uncertain

2.6

.;M;M

MutationTaster

Benign

0.000030

P;P;P;P;P;P

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.3

.;N;N

REVEL

Uncertain

0.47

Sift

Uncertain

0.015

.;D;D

Sift4G

Uncertain

0.034

D;D;D

Polyphen

0.59

P;P;P

Vest4

0.43

MPC

0.43

ClinPred

0.034

GERP RS

5.4

Varity_R

0.26

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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