Variant rs61747139 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.170

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]

MTNR1B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE
MTNR1B	NM_005959.5 linkuse as main transcript	c.728A>G	p.Lys243Arg	missense_variant	2/2	ENST00000257068.3
MTNR1B	XM_011542839.3 linkuse as main transcript	c.728A>G	p.Lys243Arg	missense_variant	2/3
MTNR1B	XM_017017777.2 linkuse as main transcript	c.602A>G	p.Lys201Arg	missense_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MTNR1B	ENST00000257068.3 linkuse as main transcript	c.728A>G	p.Lys243Arg	missense_variant	2/2	1	NM_005959.5	P1
MTNR1B	ENST00000528076.1 linkuse as main transcript	c.166-2856A>G		intron_variant		3
MTNR1B	ENST00000532482.1 linkuse as main transcript	c.*619A>G		3_prime_UTR_variant, NMD_transcript_variant	3/3	5

Frequencies

GnomAD3 genomes

AF:

0.0865

AC:

13168

AN:

152160

Hom.:

1225

Cov.:

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

GnomAD3 exomes

AF:

0.0395

AC:

9930

AN:

251458

Hom.:

572

AF XY:

0.0351

AC XY:

4769

AN XY:

135908

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 SAS exome

AF:

0.0133

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.:

AF XY:

0.0314

AC XY:

22853

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.249

Gnomad4 AMR exome

AF:

0.0229

Gnomad4 ASJ exome

AF:

0.0766

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0135

Gnomad4 FIN exome

AF:

0.0259

Gnomad4 NFE exome

AF:

0.0278

Gnomad4 OTH exome

AF:

0.0420

GnomAD4 genome

AF:

0.0866

AC:

13185

AN:

152278

Hom.:

1227

Cov.:

AF XY:

0.0836

AC XY:

6226

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.234

Gnomad4 AMR

AF:

0.0375

Gnomad4 ASJ

AF:

0.0801

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0118

Gnomad4 FIN

AF:

0.0272

Gnomad4 NFE

AF:

0.0296

Gnomad4 OTH

AF:

0.0728

Alfa

AF:

0.0556

Hom.:

284

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:

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

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 06, 2019

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

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.6

DANN

Benign

0.88

DEOGEN2

Benign

0.048

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0063

LIST_S2

Benign

0.56

MetaRNN

Benign

0.0043

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.26

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Benign

0.020

REVEL

Benign

0.060

Sift

Benign

0.77

Sift4G

Benign

0.47

Polyphen

0.0010

Vest4

0.0030

MPC

0.13

ClinPred

0.000014

GERP RS

1.1

Varity_R

0.030

gMVP

0.14

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