9-5309831-C-T

Variant names:

• chr9-5309831-C-T
• rs4742076
• ENST00000801821.1:n.260-1563G>A

Variant summary

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

The ENST00000801821.1(ENSG00000304293):​n.260-1563G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 151,640 control chromosomes in the GnomAD database, including 6,989 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 0.29 (6989 hom., cov: 31)
• Consequence: ENSG00000304293 ENST00000801821.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RLN2	XM_047423707.1	c.-337-1563G>A		intron_variant	Intron 1 of 4		XP_047279663.1
RLN2	XM_047423709.1	c.-2640-1563G>A		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.260-1563G>A		intron_variant	Intron 1 of 1
ENSG00000304293	ENST00000801822.1	n.387+1101G>A		intron_variant	Intron 2 of 2
ENSG00000304293	ENST00000801823.1	n.142+1101G>A		intron_variant	Intron 1 of 1
ENSG00000304293	ENST00000801824.1	n.88+1101G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44490 AN: 151522 Hom.: 6983 Cov.: 31

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.147

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.323

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

GnomAD4 genome AF: 0.294 AC: 44529 AN: 151640 Hom.: 6989 Cov.: 31 AF XY: 0.294 AC XY: 21823 AN XY: 74102

African (AFR) AF: 0.288 AC: 11880 AN: 41264

American (AMR) AF: 0.392 AC: 5960 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.311 AC: 1079 AN: 3464

East Asian (EAS) AF: 0.448 AC: 2300 AN: 5138

South Asian (SAS) AF: 0.397 AC: 1905 AN: 4798

European-Finnish (FIN) AF: 0.190 AC: 2007 AN: 10562

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.272 AC: 18481 AN: 67890

Other (OTH) AF: 0.322 AC: 675 AN: 2098

Alfa AF: 0.261 Hom.: 2581

Bravo AF: 0.312

Asia WGS AF: 0.415 AC: 1441 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.78
DANN	Benign	0.70
PhyloP100		-0.18

Splicing

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

Other links and lift over

dbSNP: rs4742076; hg19: chr9-5309831; COSMIC: COSV67552628;