Genetic Variant RLN3:c.-13A>G (chr19-14028192-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_080864.4(RLN3):c.-13A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.799 in 1,554,026 control chromosomes in the GnomAD database, including 498,149 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 0.84 ( 54496 hom., cov: 31)

Exomes 𝑓: 0.79 ( 443653 hom. )

Consequence

RLN3
NM_080864.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.531

Publications

23 publications found

Variant links:

Genes affected

RLN3 (HGNC:17135): (relaxin 3) This gene encodes a member of the relaxin family of insulin-like hormones that is expressed predominantly in the brain and plays a role in physiological processes such as stress, memory and appetite regulation. The encoded protein is a precursor that is proteolytically processed to generate a heterodimeric mature form consisting A and B chains interlinked by disulfide bonds. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2015]

RLN3 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080864.4. 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
	RLN3	NM_080864.4	MANE Select	c.-13A>G		5_prime_UTR	Exon 1 of 2	NP_543140.1	Q8WXF3
	RLN3	NM_001311197.2		c.-13A>G		5_prime_UTR	Exon 1 of 3	NP_001298126.1	K7ENX1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RLN3	ENST00000431365.3	TSL:1 MANE Select	c.-13A>G		5_prime_UTR	Exon 1 of 2	ENSP00000397415.2	Q8WXF3
	RLN3	ENST00000585987.1	TSL:1	c.-13A>G		upstream_gene	N/A	ENSP00000467130.1	K7ENX1

Frequencies

GnomAD3 genomes

AF:

0.843

AC:

128080

AN:

151958

Hom.:

54440

Cov.:

show subpopulations

Gnomad AFR

AF:

0.959

Gnomad AMI

AF:

0.815

Gnomad AMR

AF:

0.887

Gnomad ASJ

AF:

0.827

Gnomad EAS

AF:

0.836

Gnomad SAS

AF:

0.858

Gnomad FIN

AF:

0.685

Gnomad MID

AF:

0.905

Gnomad NFE

AF:

0.787

Gnomad OTH

AF:

0.855

GnomAD2 exomes

AF:

0.823

AC:

171396

AN:

208174

AF XY:

0.820

show subpopulations

Gnomad AFR exome

AF:

0.962

Gnomad AMR exome

AF:

0.914

Gnomad ASJ exome

AF:

0.840

Gnomad EAS exome

AF:

0.855

Gnomad FIN exome

AF:

0.691

Gnomad NFE exome

AF:

0.790

Gnomad OTH exome

AF:

0.811

GnomAD4 exome

AF:

0.794

AC:

1113521

AN:

1401950

Hom.:

443653

Cov.:

AF XY:

0.797

AC XY:

551729

AN XY:

692320

show subpopulations

African (AFR)

AF:

0.967

AC:

30545

AN:

31586

American (AMR)

AF:

0.910

AC:

32397

AN:

35616

Ashkenazi Jewish (ASJ)

AF:

0.835

AC:

18638

AN:

22308

East Asian (EAS)

AF:

0.828

AC:

32087

AN:

38744

South Asian (SAS)

AF:

0.853

AC:

66499

AN:

77960

European-Finnish (FIN)

AF:

0.700

AC:

36065

AN:

51520

Middle Eastern (MID)

AF:

0.905

AC:

4842

AN:

5350

European-Non Finnish (NFE)

AF:

0.782

AC:

845684

AN:

1081254

Other (OTH)

AF:

0.812

AC:

46764

AN:

57612

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

10123

20246

30368

40491

50614

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20522

41044

61566

82088

102610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.843

AC:

128196

AN:

152076

Hom.:

54496

Cov.:

AF XY:

0.840

AC XY:

62464

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.959

AC:

39804

AN:

41520

American (AMR)

AF:

0.888

AC:

13545

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.827

AC:

2873

AN:

3472

East Asian (EAS)

AF:

0.835

AC:

4306

AN:

5156

South Asian (SAS)

AF:

0.858

AC:

4131

AN:

4814

European-Finnish (FIN)

AF:

0.685

AC:

7240

AN:

10562

Middle Eastern (MID)

AF:

0.905

AC:

266

AN:

294

European-Non Finnish (NFE)

AF:

0.787

AC:

53495

AN:

67986

Other (OTH)

AF:

0.854

AC:

1796

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1024

2049

3073

4098

5122

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

880

1760

2640

3520

4400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.812

Hom.:

156443

Bravo

AF:

0.863

Asia WGS

AF:

0.869

AC:

3023

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.1

(source)

DANN

Benign

0.28

PhyloP100

-0.53

PromoterAI

0.011

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over