Variant 9-5339664-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_006911.4(RLN1):c.83A>T(p.Lys28Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.00054 ( 1 hom., cov: 27)

Exomes 𝑓: 0.000063 ( 5 hom. )

Failed GnomAD Quality Control

Consequence

RLN1
NM_006911.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.579

Variant links:

Genes affected

RLN1 (HGNC:10026): (relaxin 1) Relaxins are known endocrine and autocrine/paracrine hormones, belonging to the insulin gene superfamily. In humans there are three non-allelic relaxin genes, RLN1, RLN2 and RLN3, where RLN1 and RLN2 share high sequence homology. The protein encoded by this gene is synthesized as a single-chain polypeptide but the active form consists of an A chain and a B chain linked by disulfide bonds. Relaxin is produced by the ovary, and targets the mammalian reproductive system to ripen the cervix, elongate the pubic symphysis and inhibit uterine contraction. It may have additional roles in enhancing sperm motility, regulating blood pressure, controlling heart rate and releasing oxytocin and vasopressin. [provided by RefSeq, Jan 2013]

RLN1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.047902405).

BP6

Variant 9-5339664-T-A is Benign according to our data. Variant chr9-5339664-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 2363928.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RLN1	NM_006911.4 link	c.83A>T	p.Lys28Met	missense_variant	Exon 1 of 2	ENST00000223862.2	NP_008842.1	P04808-1
RLN1	XM_047423703.1 link	c.83A>T	p.Lys28Met	missense_variant	Exon 1 of 3		XP_047279659.1
RLN1	XM_047423706.1 link	c.-48+1157A>T		intron_variant	Intron 1 of 1		XP_047279662.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RLN1	ENST00000223862.2 link	c.83A>T	p.Lys28Met	missense_variant	Exon 1 of 2	1	NM_006911.4	ENSP00000223862.1		P04808-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

150470

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000330

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.000623

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000630

AC:

AN:

1460884

Hom.:

Cov.:

AF XY:

0.0000757

AC XY:

AN XY:

726742

show subpopulations

Gnomad4 AFR exome

AF:

0.000453

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000555

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000324

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000538

AC:

AN:

150584

Hom.:

Cov.:

AF XY:

0.000570

AC XY:

AN XY:

73634

show subpopulations

Gnomad4 AFR

AF:

0.00133

Gnomad4 AMR

AF:

0.000329

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000192

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 18, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.29

DANN

Benign

0.67

DEOGEN2

Benign

0.080

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.00032

LIST_S2

Benign

0.27

M_CAP

Benign

0.0023

MetaRNN

Benign

0.048

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.14

PrimateAI

Benign

0.39

PROVEAN

Benign

0.77

REVEL

Benign

0.020

Sift

Benign

0.15

Sift4G

Benign

0.11

Polyphen

0.0060

Vest4

0.12

MutPred

0.15

Loss of ubiquitination at K28 (P = 0.0309);

MVP

0.12

MPC

0.095

ClinPred

0.019

GERP RS

-1.9

Varity_R

0.090

gMVP

0.19

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