Genetic Variant MTNR1B:c.*438G>A (chr11-92982750-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_005959.5(MTNR1B):c.*438G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 204,720 control chromosomes in the GnomAD database, including 31,883 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 0.56 ( 23744 hom., cov: 31)

Exomes 𝑓: 0.54 ( 8139 hom. )

Consequence

MTNR1B
NM_005959.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.161

Publications

11 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]

MTNR1B links:

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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=-0.8).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MTNR1B	NM_005959.5 link	c.*438G>A	3_prime_UTR_variant	Exon 2 of 2	ENST00000257068.3	NP_005950.1	P49286
MTNR1B	XM_011542839.3 link	c.*411+27G>A	intron_variant	Intron 2 of 2		XP_011541141.1	P49286
MTNR1B	XM_017017777.2 link	c.*411+27G>A	intron_variant	Intron 2 of 2		XP_016873266.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTNR1B	ENST00000257068.3 link	c.*438G>A		3_prime_UTR_variant	Exon 2 of 2	1	NM_005959.5	ENSP00000257068.2		P49286
MTNR1B	ENST00000528076.1 link	c.165-2057G>A		intron_variant	Intron 1 of 1	3		ENSP00000433573.1		H0YDG4

Frequencies

GnomAD3 genomes

AF:

0.555

AC:

84199

AN:

151758

Hom.:

23704

Cov.:

show subpopulations

Gnomad AFR

AF:

0.557

Gnomad AMI

AF:

0.680

Gnomad AMR

AF:

0.655

Gnomad ASJ

AF:

0.438

Gnomad EAS

AF:

0.696

Gnomad SAS

AF:

0.694

Gnomad FIN

AF:

0.573

Gnomad MID

AF:

0.570

Gnomad NFE

AF:

0.512

Gnomad OTH

AF:

0.540

GnomAD4 exome

AF:

0.537

AC:

28386

AN:

52844

Hom.:

8139

Cov.:

AF XY:

0.546

AC XY:

14609

AN XY:

26778

show subpopulations

African (AFR)

AF:

0.535

AC:

618

AN:

1156

American (AMR)

AF:

0.701

AC:

2644

AN:

3772

Ashkenazi Jewish (ASJ)

AF:

0.407

AC:

505

AN:

1242

East Asian (EAS)

AF:

0.663

AC:

1937

AN:

2920

South Asian (SAS)

AF:

0.687

AC:

3053

AN:

4444

European-Finnish (FIN)

AF:

0.552

AC:

1576

AN:

2854

Middle Eastern (MID)

AF:

0.582

AC:

121

AN:

208

European-Non Finnish (NFE)

AF:

0.493

AC:

16385

AN:

33224

Other (OTH)

AF:

0.512

AC:

1547

AN:

3024

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

593

1186

1778

2371

2964

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

198

396

594

792

990

<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:

0.555

AC:

84302

AN:

151876

Hom.:

23744

Cov.:

AF XY:

0.563

AC XY:

41808

AN XY:

74224

show subpopulations

African (AFR)

AF:

0.557

AC:

23062

AN:

41394

American (AMR)

AF:

0.656

AC:

10016

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.438

AC:

1518

AN:

3466

East Asian (EAS)

AF:

0.697

AC:

3586

AN:

5148

South Asian (SAS)

AF:

0.694

AC:

3336

AN:

4808

European-Finnish (FIN)

AF:

0.573

AC:

6050

AN:

10556

Middle Eastern (MID)

AF:

0.572

AC:

167

AN:

292

European-Non Finnish (NFE)

AF:

0.512

AC:

34811

AN:

67924

Other (OTH)

AF:

0.540

AC:

1137

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1863

3727

5590

7454

9317

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

724

1448

2172

2896

3620

<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:

0.523

Hom.:

4369

Bravo

AF:

0.562

Asia WGS

AF:

0.649

AC:

2255

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.9

(source)

DANN

Benign

0.83

PhyloP100

0.16

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over