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GeneBe

9-5339673-G-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_006911.4(RLN1):c.74C>A(p.Ala25Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000107 in 1,460,728 control chromosomes in the GnomAD database, including 6 homozygotes. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00059 ( 2 hom., cov: 27)
Exomes 𝑓: 0.00011 ( 6 hom. )
Failed GnomAD Quality Control

Consequence

RLN1
NM_006911.4 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.16
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.05583644).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RLN1NM_006911.4 linkuse as main transcriptc.74C>A p.Ala25Asp missense_variant 1/2 ENST00000223862.2
RLN1XM_047423703.1 linkuse as main transcriptc.74C>A p.Ala25Asp missense_variant 1/3
RLN1XM_047423706.1 linkuse as main transcriptc.-48+1148C>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RLN1ENST00000223862.2 linkuse as main transcriptc.74C>A p.Ala25Asp missense_variant 1/21 NM_006911.4 P1P04808-1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
89
AN:
149918
Hom.:
2
Cov.:
27
FAILED QC
Gnomad AFR
AF:
0.00147
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000330
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00115
Gnomad SAS
AF:
0.000622
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000235
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.000107
AC:
156
AN:
1460728
Hom.:
6
Cov.:
31
AF XY:
0.000122
AC XY:
89
AN XY:
726654
show subpopulations
Gnomad4 AFR exome
AF:
0.000664
Gnomad4 AMR exome
AF:
0.000291
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000657
Gnomad4 SAS exome
AF:
0.0000581
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000738
Gnomad4 OTH exome
AF:
0.000133
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.000587
AC:
88
AN:
150038
Hom.:
2
Cov.:
27
AF XY:
0.000599
AC XY:
44
AN XY:
73416
show subpopulations
Gnomad4 AFR
AF:
0.00147
Gnomad4 AMR
AF:
0.000330
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00116
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000235
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000240
Hom.:
0
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 18, 2021The c.74C>A (p.A25D) alteration is located in exon 1 (coding exon 1) of the RLN1 gene. This alteration results from a C to A substitution at nucleotide position 74, causing the alanine (A) at amino acid position 25 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.79
Cadd
Benign
0.29
Dann
Benign
0.51
DEOGEN2
Benign
0.14
T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.5
FATHMM_MKL
Benign
0.0054
N
LIST_S2
Benign
0.24
T
M_CAP
Benign
0.0020
T
MetaRNN
Benign
0.056
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-1.0
N
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-0.66
N
REVEL
Benign
0.022
Sift
Benign
0.64
T
Sift4G
Benign
0.65
T
Polyphen
0.0
B
Vest4
0.076
MutPred
0.37
Loss of catalytic residue at A25 (P = 0.0098);
MVP
0.061
MPC
0.11
ClinPred
0.0046
T
GERP RS
-1.9
Varity_R
0.089
gMVP
0.10

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: rs764553245; hg19: chr9-5339673; API