11-92982683-G-A

Variant names:

• chr11-92982683-G-A
• rs1562444
• NM_005959.5:c.*371G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850
• Publications: 26 publications found

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005959.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTNR1B	NM_005959.5	MANE Select	c.*371G>A		3_prime_UTR	Exon 2 of 2	NP_005950.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTNR1B	ENST00000257068.3	TSL:1 MANE Select	c.*371G>A		3_prime_UTR	Exon 2 of 2	ENSP00000257068.2
	MTNR1B	ENST00000528076.1	TSL:3	c.165-2124G>A		intron	N/A	ENSP00000433573.1

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84146 AN: 151704 Hom.: 23684 Cov.: 31

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.: 0 AF XY: 0.551 AC XY: 31096 AN XY: 56454

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

GnomAD4 genome AF: 0.555 AC: 84249 AN: 151822 Hom.: 23724 Cov.: 31 AF XY: 0.563 AC XY: 41786 AN XY: 74180

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.56
PhyloP100		0.085
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

Other links and lift over

dbSNP: rs1562444; hg19: chr11-92715849;