chr9-5300385-C-G

Variant names:

• chr9-5300385-C-G
• rs148022171
• NM_134441.3:c.271G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_134441.3(RLN2):​c.271G>C​(p.Val91Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000608 in 1,612,752 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00049 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00062 (1 hom.)
• Consequence: RLN2 NM_134441.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0800
• Publications: 4 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008643895).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_134441.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RLN2	NM_134441.3	MANE Select	c.271G>C	p.Val91Leu	missense	Exon 2 of 2	NP_604390.1	P04090-1
	RLN2	NM_001329191.2		c.16G>C	p.Val6Leu	missense	Exon 2 of 2	NP_001316120.1
	RLN2	NM_005059.4		c.*18G>C		3_prime_UTR	Exon 3 of 3	NP_005050.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RLN2	ENST00000381627.4	TSL:1 MANE Select	c.271G>C	p.Val91Leu	missense	Exon 2 of 2	ENSP00000371040.3	P04090-1
	RLN2	ENST00000416837.1	TSL:3	c.*18G>C		3_prime_UTR	Exon 3 of 3	ENSP00000399616.1	H0Y5M9

Frequencies

GnomAD3 genomes AF: 0.000487 AC: 74 AN: 151920 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000590

Gnomad ASJ AF: 0.00404

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000618

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000533 AC: 133 AN: 249426 AF XY: 0.000668

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.000788

Gnomad ASJ exome AF: 0.00159

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000691

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.000620 AC: 906 AN: 1460712 Hom.: 1 Cov.: 31 AF XY: 0.000621 AC XY: 451 AN XY: 726536

African (AFR) AF: 0.000120 AC: 4 AN: 33432

American (AMR) AF: 0.000786 AC: 35 AN: 44528

Ashkenazi Jewish (ASJ) AF: 0.00207 AC: 54 AN: 26106

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.0000350 AC: 3 AN: 85732

European-Finnish (FIN) AF: 0.0000936 AC: 5 AN: 53402

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5766

European-Non Finnish (NFE) AF: 0.000657 AC: 730 AN: 1111704

Other (OTH) AF: 0.00109 AC: 66 AN: 60360

GnomAD4 genome AF: 0.000487 AC: 74 AN: 152040 Hom.: 0 Cov.: 32 AF XY: 0.000484 AC XY: 36 AN XY: 74310

African (AFR) AF: 0.000121 AC: 5 AN: 41440

American (AMR) AF: 0.000589 AC: 9 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00404 AC: 14 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10554

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000618 AC: 42 AN: 67980

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.000645 Hom.: 0

Bravo AF: 0.000552

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.000486 AC: 59

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000927

EpiControl AF: 0.00148

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	6.6
DANN	Benign	0.79
DEOGEN2	Benign	0.23	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0090	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.0086	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.040	N
PhyloP100		-0.080
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.19	N
REVEL	Benign	0.0
Sift	Benign	0.30	T
Sift4G	Benign	0.40	T
Polyphen		0.0030	B
Vest4		0.086
MVP		0.040
MPC		0.076
ClinPred		0.0011	T
GERP RS		-3.0
Varity_R		0.051
gMVP		0.052
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs148022171; hg19: chr9-5300385;