9-5311171-A-G

Position:

• chr9-5311171-A-G

Variant summary

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

The XM_047423707.1(RLN2):​c.-337-2903T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.591 in 151,762 control chromosomes in the GnomAD database, including 28,752 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 0.59 (28752 hom., cov: 32)
• Consequence: RLN2 XM_047423707.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.507

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RLN2	XM_047423707.1	c.-337-2903T>C		intron_variant			XP_047279663.1
RLN2	XM_047423709.1	c.-2640-2903T>C		intron_variant			XP_047279665.1
		n.5311171A>G		intergenic_region

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89551 AN: 151644 Hom.: 28693 Cov.: 32

Gnomad AFR AF: 0.829

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.635

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.586

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

GnomAD4 genome AF: 0.591 AC: 89674 AN: 151762 Hom.: 28752 Cov.: 32 AF XY: 0.588 AC XY: 43636 AN XY: 74156

Gnomad4 AFR AF: 0.829

Gnomad4 AMR AF: 0.609

Gnomad4 ASJ AF: 0.535

Gnomad4 EAS AF: 0.698

Gnomad4 SAS AF: 0.634

Gnomad4 FIN AF: 0.395

Gnomad4 NFE AF: 0.466

Gnomad4 OTH AF: 0.590

Alfa AF: 0.497 Hom.: 12274

Bravo AF: 0.621

Asia WGS AF: 0.699 AC: 2429 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.1
DANN	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10115467; hg19: chr9-5311171; COSMIC: COSV71422147;