9-5318770-C-A

Variant names:

• chr9-5318770-C-A
• rs10491649
• XM_047423707.1:c.-337-10502G>T

Variant summary

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

The XM_047423707.1(RLN2):​c.-337-10502G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 151,600 control chromosomes in the GnomAD database, including 12,396 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 0.39 (12396 hom., cov: 31)
• Consequence: RLN2 XM_047423707.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.533
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RLN2	XM_047423707.1	c.-337-10502G>T		intron_variant	Intron 1 of 4		XP_047279663.1
RLN2	XM_047423709.1	c.-2640-10502G>T		intron_variant	Intron 1 of 2		XP_047279665.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.395 AC: 59788 AN: 151482 Hom.: 12399 Cov.: 31

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.369

Gnomad AMR AF: 0.383

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.318

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.394 AC: 59796 AN: 151600 Hom.: 12396 Cov.: 31 AF XY: 0.395 AC XY: 29235 AN XY: 74102

African (AFR) AF: 0.300 AC: 12377 AN: 41270

American (AMR) AF: 0.382 AC: 5820 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1672 AN: 3470

East Asian (EAS) AF: 0.208 AC: 1072 AN: 5154

South Asian (SAS) AF: 0.423 AC: 2028 AN: 4792

European-Finnish (FIN) AF: 0.465 AC: 4880 AN: 10496

Middle Eastern (MID) AF: 0.322 AC: 94 AN: 292

European-Non Finnish (NFE) AF: 0.452 AC: 30682 AN: 67878

Other (OTH) AF: 0.397 AC: 835 AN: 2102

Alfa AF: 0.429 Hom.: 39704

Bravo AF: 0.377

Asia WGS AF: 0.317 AC: 1103 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.24
DANN	Benign	0.11
PhyloP100		-0.53

Splicing

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

Other links and lift over

dbSNP: rs10491649; hg19: chr9-5318770;