chr9-5311171-A-G

Variant names:

• chr9-5311171-A-G
• rs10115467
• ENST00000801821.1:n.260-2903T>C

Variant summary

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

The ENST00000801821.1(ENSG00000304293):​n.260-2903T>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: ENSG00000304293 ENST00000801821.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.507
• Publications: 9 publications found

Genes affected

ENSG00000304293 (HGNC:):

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=-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 rank	MANE	Protein	UniProt
RLN2	XM_047423707.1	c.-337-2903T>C		intron_variant	Intron 1 of 4		XP_047279663.1
RLN2	XM_047423709.1	c.-2640-2903T>C		intron_variant	Intron 1 of 2		XP_047279665.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000304293	ENST00000801821.1	n.260-2903T>C		intron_variant	Intron 1 of 1
ENSG00000304293	ENST00000801822.1	n.247-99T>C		intron_variant	Intron 1 of 2
ENSG00000304293	ENST00000801823.1	n.-98T>C		upstream_gene_variant
ENSG00000304293	ENST00000801824.1	n.-152T>C		upstream_gene_variant

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

African (AFR) AF: 0.829 AC: 34288 AN: 41346

American (AMR) AF: 0.609 AC: 9274 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 1854 AN: 3468

East Asian (EAS) AF: 0.698 AC: 3591 AN: 5142

South Asian (SAS) AF: 0.634 AC: 3041 AN: 4794

European-Finnish (FIN) AF: 0.395 AC: 4167 AN: 10562

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.466 AC: 31674 AN: 67904

Other (OTH) AF: 0.590 AC: 1245 AN: 2110

Alfa AF: 0.514 Hom.: 19501

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
PhyloP100		-0.51

Splicing

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

Other links and lift over

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