rs3758239

Positions:

• chr9-5306824-A-G

Variant summary

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

The XM_047423709.1(RLN2):​c.-1196T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 151,900 control chromosomes in the GnomAD database, including 3,687 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 0.21 (3687 hom., cov: 31)
• Consequence: RLN2 XM_047423709.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77

Genes affected

RLN2 (HGNC:10027): (relaxin 2) This gene encodes a member of the relaxin subfamily and insulin superfamily of peptide hormones. In humans there are three non-allelic relaxin genes. This gene encodes multiple protein isoforms, at least one of which undergoes proteolytic processing. This processing generates relaxin A and B chains that are linked by disulfide bonds to form the mature peptide hormone. This hormone plays a role in the male and female reproductive systems and was initially noted for its role in pregnancy. This protein also plays broader roles in the cardiovascular system, including in the regulation of blood pressure and control of heart rate, and data from animal models shows that this protein may have anti-fibrotic and cardioprotective effects. [provided by RefSeq, Jul 2016]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RLN2	XM_047423709.1	c.-1196T>C		5_prime_UTR_variant	2/3		XP_047279665.1
RLN2	XM_047423707.1	c.-62-1076T>C		intron_variant			XP_047279663.1
		n.5306824A>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32380 AN: 151780 Hom.: 3680 Cov.: 31

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.213 AC: 32422 AN: 151900 Hom.: 3687 Cov.: 31 AF XY: 0.213 AC XY: 15785 AN XY: 74222

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.180

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.190

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.193

Gnomad4 NFE AF: 0.185

Gnomad4 OTH AF: 0.210

Alfa AF: 0.190 Hom.: 5775

Bravo AF: 0.214

Asia WGS AF: 0.234 AC: 814 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.9
DANN	Benign	0.56

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3758239; hg19: chr9-5306824;