1-37612628-A-G

Position:

• chr1-37612628-A-G

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.*127T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 962,682 control chromosomes in the GnomAD database, including 130,175 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.46 (17192 hom., cov: 32)
  • Exomes 𝑓: 0.52 (112983 hom.)
• Consequence: RSPO1 NM_001242908.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.134

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=-0.83).
• BP6: Variant 1-37612628-A-G is Benign according to our data. Variant chr1-37612628-A-G is described in ClinVar as [Benign]. Clinvar id is 1276443.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RSPO1	NM_001242908.2	c.*127T>C		3_prime_UTR_variant	7/7	ENST00000356545.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RSPO1	ENST00000356545.7	c.*127T>C		3_prime_UTR_variant	7/7	1	NM_001242908.2	P1
RSPO1	ENST00000401068.1	c.*127T>C		3_prime_UTR_variant	8/8	1		P1
RSPO1	ENST00000612451.4	c.*127T>C		3_prime_UTR_variant	6/6	1
RSPO1	ENST00000615459.4	c.*127T>C		3_prime_UTR_variant	7/7	2

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69165 AN: 151840 Hom.: 17167 Cov.: 32

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.663

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.487

GnomAD4 exome AF: 0.522 AC: 422958 AN: 810724 Hom.: 112983 Cov.: 11 AF XY: 0.518 AC XY: 218776 AN XY: 422408

Gnomad4 AFR exome AF: 0.240

Gnomad4 AMR exome AF: 0.613

Gnomad4 ASJ exome AF: 0.425

Gnomad4 EAS exome AF: 0.676

Gnomad4 SAS exome AF: 0.447

Gnomad4 FIN exome AF: 0.598

Gnomad4 NFE exome AF: 0.526

Gnomad4 OTH exome AF: 0.503

GnomAD4 genome AF: 0.456 AC: 69220 AN: 151958 Hom.: 17192 Cov.: 32 AF XY: 0.460 AC XY: 34167 AN XY: 74278

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.555

Gnomad4 ASJ AF: 0.419

Gnomad4 EAS AF: 0.664

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.599

Gnomad4 NFE AF: 0.524

Gnomad4 OTH AF: 0.491

Alfa AF: 0.500 Hom.: 24129

Bravo AF: 0.442

Asia WGS AF: 0.589 AC: 2049 AN: 3478

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

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.0
DANN	Benign	0.53

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: rs4652964; hg19: chr1-38078300; COSMIC: COSV62973812;