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GeneBe

9-5339664-T-A

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 same amino acid change has been previously reported as Likely benignin 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

19

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]

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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/exons MANE UniProt
RLN1NM_006911.4 linkuse as main transcriptc.83A>T p.Lys28Met missense_variant 1/2 ENST00000223862.2
RLN1XM_047423703.1 linkuse as main transcriptc.83A>T p.Lys28Met missense_variant 1/3
RLN1XM_047423706.1 linkuse as main transcriptc.-48+1157A>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RLN1ENST00000223862.2 linkuse as main transcriptc.83A>T p.Lys28Met missense_variant 1/21 NM_006911.4 P1P04808-1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
82
AN:
150470
Hom.:
1
Cov.:
27
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:
92
AN:
1460884
Hom.:
5
Cov.:
31
AF XY:
0.0000757
AC XY:
55
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:
81
AN:
150584
Hom.:
1
Cov.:
27
AF XY:
0.000570
AC XY:
42
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.:
0

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 submitterclinical testingAmbry GeneticsAug 18, 2021This 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
T
BayesDel_noAF
Benign
-0.77
Cadd
Benign
0.29
Dann
Benign
0.67
DEOGEN2
Benign
0.080
T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.00032
N
LIST_S2
Benign
0.27
T
M_CAP
Benign
0.0023
T
MetaRNN
Benign
0.048
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.14
N
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.39
T
PROVEAN
Benign
0.77
N
REVEL
Benign
0.020
Sift
Benign
0.15
T
Sift4G
Benign
0.11
T
Polyphen
0.0060
B
Vest4
0.12
MutPred
0.15
Loss of ubiquitination at K28 (P = 0.0309);
MVP
0.12
MPC
0.095
ClinPred
0.019
T
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.

Other links and lift over

dbSNP: rs397780021; hg19: chr9-5339664; API