rs61747139

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_005959.5(MTNR1B):​c.728A>G​(p.Lys243Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0377 in 1,614,164 control chromosomes in the GnomAD database, including 2,997 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 Benign (no stars).

Frequency

Genomes: 𝑓 0.087 ( 1227 hom., cov: 33)
Exomes 𝑓: 0.033 ( 1770 hom. )

Consequence

MTNR1B
NM_005959.5 missense

Scores

18

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.170

Publications

19 publications found
Variant links:
Genes affected
MTNR1B (HGNC:7464): (melatonin receptor 1B) This gene encodes one of two high affinity forms of a receptor for melatonin, the primary hormone secreted by the pineal gland. This gene product is an integral membrane protein that is a G-protein coupled, 7-transmembrane receptor. It is found primarily in the retina and brain although this detection requires RT-PCR. It is thought to participate in light-dependent functions in the retina and may be involved in the neurobiological effects of melatonin. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.00430429).
BP6
Variant 11-92981951-A-G is Benign according to our data. Variant chr11-92981951-A-G is described in ClinVar as [Benign]. Clinvar id is 3060517.Status of the report is no_assertion_criteria_provided, 0 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MTNR1BNM_005959.5 linkc.728A>G p.Lys243Arg missense_variant Exon 2 of 2 ENST00000257068.3 NP_005950.1 P49286
MTNR1BXM_011542839.3 linkc.728A>G p.Lys243Arg missense_variant Exon 2 of 3 XP_011541141.1 P49286
MTNR1BXM_017017777.2 linkc.602A>G p.Lys201Arg missense_variant Exon 2 of 3 XP_016873266.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MTNR1BENST00000257068.3 linkc.728A>G p.Lys243Arg missense_variant Exon 2 of 2 1 NM_005959.5 ENSP00000257068.2 P49286
MTNR1BENST00000532482.1 linkn.*619A>G non_coding_transcript_exon_variant Exon 3 of 3 5 ENSP00000436101.1 E9PR36
MTNR1BENST00000532482.1 linkn.*619A>G 3_prime_UTR_variant Exon 3 of 3 5 ENSP00000436101.1 E9PR36
MTNR1BENST00000528076.1 linkc.165-2856A>G intron_variant Intron 1 of 1 3 ENSP00000433573.1 H0YDG4

Frequencies

GnomAD3 genomes
AF:
0.0865
AC:
13168
AN:
152160
Hom.:
1225
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.235
Gnomad AMI
AF:
0.0724
Gnomad AMR
AF:
0.0376
Gnomad ASJ
AF:
0.0801
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.0118
Gnomad FIN
AF:
0.0272
Gnomad MID
AF:
0.0601
Gnomad NFE
AF:
0.0297
Gnomad OTH
AF:
0.0736
GnomAD2 exomes
AF:
0.0395
AC:
9930
AN:
251458
AF XY:
0.0351
show subpopulations
Gnomad AFR exome
AF:
0.235
Gnomad AMR exome
AF:
0.0206
Gnomad ASJ exome
AF:
0.0762
Gnomad EAS exome
AF:
0.000109
Gnomad FIN exome
AF:
0.0292
Gnomad NFE exome
AF:
0.0297
Gnomad OTH exome
AF:
0.0327
GnomAD4 exome
AF:
0.0326
AC:
47627
AN:
1461886
Hom.:
1770
Cov.:
31
AF XY:
0.0314
AC XY:
22853
AN XY:
727244
show subpopulations
African (AFR)
AF:
0.249
AC:
8324
AN:
33480
American (AMR)
AF:
0.0229
AC:
1024
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.0766
AC:
2003
AN:
26136
East Asian (EAS)
AF:
0.000151
AC:
6
AN:
39698
South Asian (SAS)
AF:
0.0135
AC:
1164
AN:
86258
European-Finnish (FIN)
AF:
0.0259
AC:
1382
AN:
53416
Middle Eastern (MID)
AF:
0.0569
AC:
328
AN:
5768
European-Non Finnish (NFE)
AF:
0.0278
AC:
30861
AN:
1112010
Other (OTH)
AF:
0.0420
AC:
2535
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.488
Heterozygous variant carriers
0
3240
6480
9719
12959
16199
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
1276
2552
3828
5104
6380
<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:
0.0866
AC:
13185
AN:
152278
Hom.:
1227
Cov.:
33
AF XY:
0.0836
AC XY:
6226
AN XY:
74472
show subpopulations
African (AFR)
AF:
0.234
AC:
9734
AN:
41524
American (AMR)
AF:
0.0375
AC:
574
AN:
15306
Ashkenazi Jewish (ASJ)
AF:
0.0801
AC:
278
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5178
South Asian (SAS)
AF:
0.0118
AC:
57
AN:
4830
European-Finnish (FIN)
AF:
0.0272
AC:
289
AN:
10616
Middle Eastern (MID)
AF:
0.0544
AC:
16
AN:
294
European-Non Finnish (NFE)
AF:
0.0296
AC:
2017
AN:
68034
Other (OTH)
AF:
0.0728
AC:
154
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
561
1121
1682
2242
2803
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
130
260
390
520
650
<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:
0.0561
Hom.:
397
Bravo
AF:
0.0947
TwinsUK
AF:
0.0337
AC:
125
ALSPAC
AF:
0.0288
AC:
111
ESP6500AA
AF:
0.235
AC:
1033
ESP6500EA
AF:
0.0330
AC:
284
ExAC
AF:
0.0421
AC:
5116
Asia WGS
AF:
0.0190
AC:
67
AN:
3478
EpiCase
AF:
0.0347
EpiControl
AF:
0.0294

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

MTNR1B-related disorder Benign:1
Nov 06, 2019
PreventionGenetics, part of Exact Sciences
Significance:Benign
Review Status:no assertion criteria provided
Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.081
BayesDel_addAF
Benign
-0.81
T
BayesDel_noAF
Benign
-0.80
CADD
Benign
4.6
DANN
Benign
0.88
DEOGEN2
Benign
0.048
T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.0063
N
LIST_S2
Benign
0.56
T
MetaRNN
Benign
0.0043
T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.26
N
PhyloP100
0.17
PrimateAI
Benign
0.29
T
PROVEAN
Benign
0.020
N
REVEL
Benign
0.060
Sift
Benign
0.77
T
Sift4G
Benign
0.47
T
Polyphen
0.0010
B
Vest4
0.0030
MPC
0.13
ClinPred
0.000014
T
GERP RS
1.1
Varity_R
0.030
gMVP
0.14
Mutation Taster
=99/1
polymorphism (auto)

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

Other links and lift over

dbSNP: rs61747139; hg19: chr11-92715117; API