rs2346793

Variant names:

• chr4-158444532-G-T
• rs2346793
• ENST00000460056.6:c.-289+22164G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000460056.6(RXFP1):​c.-289+22164G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,202 control chromosomes in the GnomAD database, including 3,625 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 0.20 (3625 hom., cov: 33)
• Consequence: RXFP1 ENST00000460056.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.297 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.-289+22164G>T		intron_variant	Intron 2 of 19	2		ENSP00000423306.1

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30698 AN: 152084 Hom.: 3614 Cov.: 33

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.0131

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.201

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

GnomAD4 genome AF: 0.202 AC: 30734 AN: 152202 Hom.: 3625 Cov.: 33 AF XY: 0.200 AC XY: 14907 AN XY: 74414

African (AFR) AF: 0.301 AC: 12521 AN: 41534

American (AMR) AF: 0.234 AC: 3581 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 629 AN: 3472

East Asian (EAS) AF: 0.0131 AC: 68 AN: 5176

South Asian (SAS) AF: 0.198 AC: 955 AN: 4822

European-Finnish (FIN) AF: 0.143 AC: 1521 AN: 10602

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10867 AN: 67996

Other (OTH) AF: 0.200 AC: 423 AN: 2114

Alfa AF: 0.176 Hom.: 457

Bravo AF: 0.212

Asia WGS AF: 0.151 AC: 524 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.73
DANN	Benign	0.57
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2346793; hg19: chr4-159365684;