Genetic Variant NM_080864.4: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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RLN3	NM_080864.4 link	c.-13A>G		5_prime_UTR_variant	Exon 1 of 2	ENST00000431365.3	NP_543140.1	Q8WXF3B2RU28
RLN3	NM_001311197.2 link	c.-13A>G		5_prime_UTR_variant	Exon 1 of 3		NP_001298126.1	Q8WXF3K7ENX1B2RU28

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RLN3	ENST00000431365.3 link	c.-13A>G		5_prime_UTR_variant	Exon 1 of 2	1	NM_080864.4	ENSP00000397415.2		Q8WXF3
RLN3	ENST00000585987.1 link	c.-13A>G		upstream_gene_variant		1		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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over