11-92984961-G-C

Variant names:

• chr11-92984961-G-C
• rs1447350
• ENST00000528076.1:c.319G>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000528076.1(MTNR1B):​c.319G>C​(p.Ala107Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 455,190 control chromosomes in the GnomAD database, including 75,410 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict 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 (23097 hom., cov: 33)
  • Exomes 𝑓: 0.58 (52313 hom.)
• Consequence: MTNR1B ENST00000528076.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 13 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.031).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000528076.1. 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTNR1B	ENST00000528076.1	TSL:3	c.319G>C	p.Ala107Pro	missense	Exon 2 of 2	ENSP00000433573.1

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83066 AN: 151958 Hom.: 23069 Cov.: 33

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.440

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.535

GnomAD2 exomes AF: 0.602 AC: 76807 AN: 127482 AF XY: 0.601

Gnomad AFR exome AF: 0.517

Gnomad AMR exome AF: 0.749

Gnomad ASJ exome AF: 0.433

Gnomad EAS exome AF: 0.682

Gnomad FIN exome AF: 0.586

Gnomad NFE exome AF: 0.517

Gnomad OTH exome AF: 0.565

GnomAD4 exome AF: 0.578 AC: 175160 AN: 303114 Hom.: 52313 Cov.: 0 AF XY: 0.586 AC XY: 101164 AN XY: 172576

African (AFR) AF: 0.518 AC: 4445 AN: 8574

American (AMR) AF: 0.747 AC: 20289 AN: 27168

Ashkenazi Jewish (ASJ) AF: 0.432 AC: 4635 AN: 10726

East Asian (EAS) AF: 0.684 AC: 6299 AN: 9206

South Asian (SAS) AF: 0.682 AC: 40537 AN: 59396

European-Finnish (FIN) AF: 0.581 AC: 7177 AN: 12356

Middle Eastern (MID) AF: 0.558 AC: 1551 AN: 2780

European-Non Finnish (NFE) AF: 0.519 AC: 82372 AN: 158714

Other (OTH) AF: 0.553 AC: 7855 AN: 14194

GnomAD4 genome AF: 0.547 AC: 83154 AN: 152076 Hom.: 23097 Cov.: 33 AF XY: 0.556 AC XY: 41288 AN XY: 74320

African (AFR) AF: 0.522 AC: 21663 AN: 41486

American (AMR) AF: 0.653 AC: 9985 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.440 AC: 1525 AN: 3468

East Asian (EAS) AF: 0.695 AC: 3584 AN: 5154

South Asian (SAS) AF: 0.687 AC: 3311 AN: 4822

European-Finnish (FIN) AF: 0.575 AC: 6080 AN: 10566

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.516 AC: 35086 AN: 67972

Other (OTH) AF: 0.535 AC: 1131 AN: 2114

Alfa AF: 0.446 Hom.: 2144

Bravo AF: 0.552

Asia WGS AF: 0.648 AC: 2251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.20
DANN	Benign	0.35
PhyloP100		-1.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1447350; hg19: chr11-92718127;