rs10517691

Variant names:

• chr4-158477994-A-G
• rs10517691
• ENST00000460056.6:c.-288-36851A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000460056.6(RXFP1):​c.-288-36851A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,156 control chromosomes in the GnomAD database, including 1,462 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1462 hom., cov: 32)
• Consequence: RXFP1 ENST00000460056.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.547

Genes affected

RXFP1 (HGNC:19718): (relaxin family peptide receptor 1) This gene encodes a member of the leucine-rich repeat-containing subgroup of the G protein-coupled 7-transmembrane receptor superfamily. The encoded protein plays a critical role in sperm motility, pregnancy and parturition as a receptor for the protein hormone relaxin. Decreased expression of this gene may play a role in endometriosis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RXFP1	ENST00000460056.6	c.-288-36851A>G		intron_variant	Intron 2 of 19	2		ENSP00000423306.1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20386 AN: 152038 Hom.: 1458 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.0410

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.0723

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.143

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.134 AC: 20409 AN: 152156 Hom.: 1462 Cov.: 32 AF XY: 0.133 AC XY: 9932 AN XY: 74404

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.0413

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.0723

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.140

Alfa AF: 0.142 Hom.: 2147

Bravo AF: 0.137

Asia WGS AF: 0.103 AC: 358 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10517691; hg19: chr4-159399146;