XM_047423709.1:c.-1196T>C

Variant names:

• chr9-5306824-A-G
• rs3758239
• XM_047423709.1:c.-1196T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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]

ENSG00000304317 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RLN2	XM_047423709.1	c.-1196T>C		5_prime_UTR_variant	Exon 2 of 3		XP_047279665.1
RLN2	XM_047423707.1	c.-62-1076T>C		intron_variant	Intron 2 of 4		XP_047279663.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000304317	ENST00000802521.1	n.189-1350A>G		intron_variant	Intron 1 of 1

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

African (AFR) AF: 0.281 AC: 11629 AN: 41360

American (AMR) AF: 0.180 AC: 2750 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 703 AN: 3470

East Asian (EAS) AF: 0.190 AC: 980 AN: 5166

South Asian (SAS) AF: 0.218 AC: 1046 AN: 4800

European-Finnish (FIN) AF: 0.193 AC: 2036 AN: 10574

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.185 AC: 12543 AN: 67964

Other (OTH) AF: 0.210 AC: 442 AN: 2104

Alfa AF: 0.193 Hom.: 12951

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
PhyloP100		1.8

Splicing

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

Other links and lift over

dbSNP: rs3758239; hg19: chr9-5306824;