dbSNP rs1562444: MTNR1B:c.*371G>A (chr11-92982683-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.*371G>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 0.551 in 261,800 control chromosomes in the GnomAD database, including 40,745 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 0.55 ( 23724 hom., cov: 31)

Exomes 𝑓: 0.55 ( 17021 hom. )

Consequence

MTNR1B
NM_005959.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0850

Publications

26 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=-0.91).

BA1

GnomAd4 highest subpopulation (SAS) 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.*371G>A	3_prime_UTR_variant	Exon 2 of 2	ENST00000257068.3	NP_005950.1	P49286
MTNR1B	XM_011542839.3 link	c.*371G>A	3_prime_UTR_variant	Exon 2 of 3		XP_011541141.1	P49286
MTNR1B	XM_017017777.2 link	c.*371G>A	3_prime_UTR_variant	Exon 2 of 3		XP_016873266.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTNR1B	ENST00000257068.3 link	c.*371G>A		3_prime_UTR_variant	Exon 2 of 2	1	NM_005959.5	ENSP00000257068.2		P49286
MTNR1B	ENST00000528076.1 link	c.165-2124G>A		intron_variant	Intron 1 of 1	3		ENSP00000433573.1		H0YDG4

Frequencies

GnomAD3 genomes

AF:

0.555

AC:

84146

AN:

151704

Hom.:

23684

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:

0.697

Gnomad FIN

AF:

0.573

Gnomad MID

AF:

0.570

Gnomad NFE

AF:

0.512

Gnomad OTH

AF:

0.538

GnomAD4 exome

AF:

0.545

AC:

59966

AN:

109978

Hom.:

17021

Cov.:

AF XY:

0.551

AC XY:

31096

AN XY:

56454

show subpopulations

African (AFR)

AF:

0.558

AC:

1818

AN:

3256

American (AMR)

AF:

0.701

AC:

3611

AN:

5154

Ashkenazi Jewish (ASJ)

AF:

0.433

AC:

1393

AN:

3218

East Asian (EAS)

AF:

0.667

AC:

4800

AN:

7198

South Asian (SAS)

AF:

0.709

AC:

4742

AN:

6688

European-Finnish (FIN)

AF:

0.562

AC:

4132

AN:

7352

Middle Eastern (MID)

AF:

0.549

AC:

269

AN:

490

European-Non Finnish (NFE)

AF:

0.509

AC:

35628

AN:

70022

Other (OTH)

AF:

0.541

AC:

3573

AN:

6600

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1280

2560

3840

5120

6400

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

280

560

840

1120

1400

<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:

84249

AN:

151822

Hom.:

23724

Cov.:

AF XY:

0.563

AC XY:

41786

AN XY:

74180

show subpopulations

African (AFR)

AF:

0.557

AC:

23069

AN:

41388

American (AMR)

AF:

0.655

AC:

10007

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.438

AC:

1518

AN:

3466

East Asian (EAS)

AF:

0.696

AC:

3564

AN:

5118

South Asian (SAS)

AF:

0.697

AC:

3350

AN:

4804

European-Finnish (FIN)

AF:

0.573

AC:

6051

AN:

10552

Middle Eastern (MID)

AF:

0.572

AC:

167

AN:

292

European-Non Finnish (NFE)

AF:

0.512

AC:

34770

AN:

67918

Other (OTH)

AF:

0.538

AC:

1134

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1879

3759

5638

7518

9397

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:

0.519

Hom.:

5050

Bravo

AF:

0.562

Asia WGS

AF:

0.651

AC:

2263

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.1

(source)

DANN

Benign

0.56

PhyloP100

0.085

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