4-186540552-G-A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005958.4(MTNR1A):​c.185-5995C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 152,134 control chromosomes in the GnomAD database, including 29,161 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.60 ( 29161 hom., cov: 34)

Consequence

MTNR1A
NM_005958.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.02

Publications

16 publications found
Variant links:
Genes affected
MTNR1A (HGNC:7463): (melatonin receptor 1A) This gene encodes one of two high affinity forms of a receptor for melatonin, the primary hormone secreted by the pineal gland. This receptor is a G-protein coupled, 7-transmembrane receptor that is responsible for melatonin effects on mammalian circadian rhythm and reproductive alterations affected by day length. The receptor is an integral membrane protein that is readily detectable and localized to two specific regions of the brain. The hypothalamic suprachiasmatic nucleus appears to be involved in circadian rhythm while the hypophysial pars tuberalis may be responsible for the reproductive 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 -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.96).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MTNR1ANM_005958.4 linkc.185-5995C>T intron_variant Intron 1 of 1 ENST00000307161.5 NP_005949.1 P48039
LOC105377596XR_007058498.1 linkn.144-5092G>A intron_variant Intron 2 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MTNR1AENST00000307161.5 linkc.185-5995C>T intron_variant Intron 1 of 1 1 NM_005958.4 ENSP00000302811.5 P48039
ENSG00000272297ENST00000509111.2 linkc.145+14630C>T intron_variant Intron 1 of 1 3 ENSP00000422449.2 H0Y8X5

Frequencies

GnomAD3 genomes
AF:
0.599
AC:
90996
AN:
152016
Hom.:
29163
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.394
Gnomad AMI
AF:
0.529
Gnomad AMR
AF:
0.625
Gnomad ASJ
AF:
0.620
Gnomad EAS
AF:
0.346
Gnomad SAS
AF:
0.406
Gnomad FIN
AF:
0.707
Gnomad MID
AF:
0.699
Gnomad NFE
AF:
0.731
Gnomad OTH
AF:
0.634
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.598
AC:
91019
AN:
152134
Hom.:
29161
Cov.:
34
AF XY:
0.593
AC XY:
44067
AN XY:
74354
show subpopulations
African (AFR)
AF:
0.394
AC:
16325
AN:
41486
American (AMR)
AF:
0.624
AC:
9536
AN:
15288
Ashkenazi Jewish (ASJ)
AF:
0.620
AC:
2151
AN:
3468
East Asian (EAS)
AF:
0.346
AC:
1790
AN:
5168
South Asian (SAS)
AF:
0.406
AC:
1959
AN:
4822
European-Finnish (FIN)
AF:
0.707
AC:
7490
AN:
10590
Middle Eastern (MID)
AF:
0.694
AC:
204
AN:
294
European-Non Finnish (NFE)
AF:
0.732
AC:
49738
AN:
67992
Other (OTH)
AF:
0.636
AC:
1345
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
1733
3466
5199
6932
8665
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
738
1476
2214
2952
3690
<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:
0.684
Hom.:
157845
Bravo
AF:
0.584
Asia WGS
AF:
0.409
AC:
1422
AN:
3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.96
CADD
Benign
0.99
DANN
Benign
0.71
PhyloP100
-1.0
Mutation Taster
=100/0
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: rs2165666; hg19: chr4-187461706; API