Variant chr11-92981559-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_005959.5(MTNR1B):c.336C>T(p.His112=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000146 in 1,614,198 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00088 ( 1 hom., cov: 33)

Exomes 𝑓: 0.000069 ( 0 hom. )

Consequence

MTNR1B
NM_005959.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.606

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 11-92981559-C-T is Benign according to our data. Variant chr11-92981559-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3056447.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.606 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MTNR1B	NM_005959.5 linkuse as main transcript	c.336C>T	p.His112=	synonymous_variant	2/2	ENST00000257068.3
MTNR1B	XM_011542839.3 linkuse as main transcript	c.336C>T	p.His112=	synonymous_variant	2/3
MTNR1B	XM_017017777.2 linkuse as main transcript	c.210C>T	p.His70=	synonymous_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MTNR1B	ENST00000257068.3 linkuse as main transcript	c.336C>T	p.His112=	synonymous_variant	2/2	1	NM_005959.5	P1
MTNR1B	ENST00000528076.1 linkuse as main transcript	c.166-3248C>T		intron_variant		3
MTNR1B	ENST00000532482.1 linkuse as main transcript	c.*227C>T		3_prime_UTR_variant, NMD_transcript_variant	3/3	5

Frequencies

GnomAD3 genomes

AF:

0.000880

AC:

134

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00316

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000239

AC:

AN:

251468

Hom.:

AF XY:

0.000155

AC XY:

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.00326

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.0000691

AC:

101

AN:

1461890

Hom.:

Cov.:

AF XY:

0.0000550

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00242

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.000248

GnomAD4 genome

AF:

0.000880

AC:

134

AN:

152308

Hom.:

Cov.:

AF XY:

0.000873

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00315

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000503

Hom.:

Bravo

AF:

0.000884

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

MTNR1B-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 01, 2019

This variant is classified as likely 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

BayesDel_noAF

Benign

-0.53

CADD

Benign

2.9

DANN

Benign

0.29

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