Variant chr19-14028292-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_080864.4(RLN3):c.88T>C(p.Tyr30His) variant causes a missense change. The variant allele was found at a frequency of 0.00415 in 1,613,784 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0026 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0043 ( 22 hom. )

Consequence

RLN3
NM_080864.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.34

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 made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011486739).

BP6

Variant 19-14028292-T-C is Benign according to our data. Variant chr19-14028292-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 787603.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RLN3	NM_080864.4 linkuse as main transcript	c.88T>C	p.Tyr30His	missense_variant	1/2	ENST00000431365.3
RLN3	NM_001311197.2 linkuse as main transcript	c.88T>C	p.Tyr30His	missense_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RLN3	ENST00000431365.3 linkuse as main transcript	c.88T>C	p.Tyr30His	missense_variant	1/2	1	NM_080864.4	P1
RLN3	ENST00000585987.1 linkuse as main transcript	c.88T>C	p.Tyr30His	missense_variant	1/3	1

Frequencies

GnomAD3 genomes

AF:

0.00259

AC:

393

AN:

152016

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000894

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00302

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00418

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00318

AC:

797

AN:

250950

Hom.:

AF XY:

0.00326

AC XY:

442

AN XY:

135706

show subpopulations

Gnomad AFR exome

AF:

0.000864

Gnomad AMR exome

AF:

0.00110

Gnomad ASJ exome

AF:

0.00109

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00173

Gnomad FIN exome

AF:

0.00264

Gnomad NFE exome

AF:

0.00536

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00431

AC:

6300

AN:

1461650

Hom.:

Cov.:

AF XY:

0.00422

AC XY:

3067

AN XY:

727130

show subpopulations

Gnomad4 AFR exome

AF:

0.000717

Gnomad4 AMR exome

AF:

0.00136

Gnomad4 ASJ exome

AF:

0.00115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00168

Gnomad4 FIN exome

AF:

0.00323

Gnomad4 NFE exome

AF:

0.00510

Gnomad4 OTH exome

AF:

0.00316

GnomAD4 genome

AF:

0.00258

AC:

393

AN:

152134

Hom.:

Cov.:

AF XY:

0.00256

AC XY:

190

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.000891

Gnomad4 AMR

AF:

0.00164

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00302

Gnomad4 NFE

AF:

0.00418

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00394

Hom.:

Bravo

AF:

0.00257

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00453

AC:

ExAC

AF:

0.00351

AC:

426

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00382

EpiControl

AF:

0.00456

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 13, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Uncertain

-0.060

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.63

D;.

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.71

T;T

M_CAP

Benign

0.075

MetaRNN

Benign

0.011

T;T

MetaSVM

Uncertain

0.20

MutationAssessor

Benign

2.0

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-4.2

D;.

REVEL

Uncertain

0.55

Sift

Pathogenic

0.0

D;.

Sift4G

Pathogenic

0.0

D;T

Polyphen

1.0

D;.

Vest4

0.52

MVP

0.81

MPC

0.38

ClinPred

0.031

GERP RS

4.6

Varity_R

0.89

gMVP

0.56

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over