chr1-37612499-G-GGTGT

Position:

• chr1-37612499-G-GGTGT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001242908.2(RSPO1):​c.*255_*256insACAC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4267 hom., cov: 0)
  • Exomes 𝑓: 0.23 (1966 hom.)
• Consequence: RSPO1 NM_001242908.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.314

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 -10 ACMG points.

• BP6: Variant 1-37612499-G-GGTGT is Benign according to our data. Variant chr1-37612499-G-GGTGT is described in ClinVar as [Benign]. Clinvar id is 1233166.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RSPO1	NM_001242908.2	c.*255_*256insACAC		3_prime_UTR_variant	7/7	ENST00000356545.7	NP_001229837.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RSPO1	ENST00000356545.7	c.*255_*256insACAC		3_prime_UTR_variant	7/7	1	NM_001242908.2	ENSP00000348944	P1
RSPO1	ENST00000401068.1	c.*255_*256insACAC		3_prime_UTR_variant	8/8	1		ENSP00000383846	P1
RSPO1	ENST00000612451.4	c.*255_*256insACAC		3_prime_UTR_variant	6/6	1		ENSP00000479832
RSPO1	ENST00000615459.4	c.*255_*256insACAC		3_prime_UTR_variant	7/7	2		ENSP00000481178

Frequencies

GnomAD3 genomes AF: 0.233 AC: 34976 AN: 149880 Hom.: 4271 Cov.: 0

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.244

GnomAD4 exome AF: 0.233 AC: 82354 AN: 354022 Hom.: 1966 Cov.: 0 AF XY: 0.233 AC XY: 43308 AN XY: 186070

Gnomad4 AFR exome AF: 0.139

Gnomad4 AMR exome AF: 0.278

Gnomad4 ASJ exome AF: 0.279

Gnomad4 EAS exome AF: 0.293

Gnomad4 SAS exome AF: 0.220

Gnomad4 FIN exome AF: 0.188

Gnomad4 NFE exome AF: 0.232

Gnomad4 OTH exome AF: 0.234

GnomAD4 genome AF: 0.233 AC: 34964 AN: 149978 Hom.: 4267 Cov.: 0 AF XY: 0.232 AC XY: 17004 AN XY: 73158

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.341

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.242

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 21, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs139353088; hg19: chr1-38078171;