Variant 1-37612828-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001242908.2(RSPO1):c.719G>A(p.Arg240Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000963 in 1,613,716 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0051 ( 10 hom., cov: 33)

Exomes 𝑓: 0.00053 ( 10 hom. )

Consequence

RSPO1
NM_001242908.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.22

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0058378577).

BP6

Variant 1-37612828-C-T is Benign according to our data. Variant chr1-37612828-C-T is described in ClinVar as [Benign]. Clinvar id is 707224.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00508 (774/152280) while in subpopulation AFR AF= 0.0178 (740/41550). AF 95% confidence interval is 0.0167. There are 10 homozygotes in gnomad4. There are 365 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RSPO1	NM_001242908.2 linkuse as main transcript	c.719G>A	p.Arg240Gln	missense_variant	7/7	ENST00000356545.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSPO1	ENST00000356545.7 linkuse as main transcript	c.719G>A	p.Arg240Gln	missense_variant	7/7	1	NM_001242908.2	P1	Q2MKA7-1
RSPO1	ENST00000401068.1 linkuse as main transcript	c.719G>A	p.Arg240Gln	missense_variant	8/8	1		P1	Q2MKA7-1
RSPO1	ENST00000612451.4 linkuse as main transcript	c.530G>A	p.Arg177Gln	missense_variant	6/6	1			Q2MKA7-3
RSPO1	ENST00000615459.4 linkuse as main transcript	c.638G>A	p.Arg213Gln	missense_variant	7/7	2			Q2MKA7-2

Frequencies

GnomAD3 genomes

AF:

0.00507

AC:

772

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0178

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00126

AC:

314

AN:

249218

Hom.:

AF XY:

0.000902

AC XY:

122

AN XY:

135268

show subpopulations

Gnomad AFR exome

AF:

0.0178

Gnomad AMR exome

AF:

0.000811

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000441

Gnomad OTH exome

AF:

0.000825

GnomAD4 exome

AF:

0.000534

AC:

780

AN:

1461436

Hom.:

Cov.:

AF XY:

0.000444

AC XY:

323

AN XY:

727064

show subpopulations

Gnomad4 AFR exome

AF:

0.0191

Gnomad4 AMR exome

AF:

0.000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.00129

GnomAD4 genome

AF:

0.00508

AC:

774

AN:

152280

Hom.:

Cov.:

AF XY:

0.00490

AC XY:

365

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0178

Gnomad4 AMR

AF:

0.00176

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00264

Hom.:

Bravo

AF:

0.00613

ESP6500AA

AF:

0.0182

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00148

AC:

179

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 15, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

.;.;T;T

Eigen

Benign

-0.19

Eigen_PC

Benign

0.010

FATHMM_MKL

Benign

0.75

LIST_S2

Uncertain

0.87

D;D;.;D

MetaRNN

Benign

0.0058

T;T;T;T

MetaSVM

Benign

-0.64

MutationAssessor

Benign

1.0

.;.;L;L

MutationTaster

Benign

0.91

D;D;D;D;N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.97

.;.;N;N

REVEL

Benign

0.14

Sift

Benign

0.041

.;.;D;D

Sift4G

Uncertain

0.031

D;T;D;D

Polyphen

0.27

B;.;B;B

Vest4

0.13

MVP

0.85

MPC

0.35

ClinPred

0.014

GERP RS

5.0

Varity_R

0.14

gMVP

0.33

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