11-92984961-G-C

Position:

• chr11-92984961-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong 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. 4/4 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

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTNR1B	XM_011542839.3	c.*566G>C		downstream_gene_variant			XP_011541141.1
MTNR1B	XM_017017777.2	c.*566G>C		downstream_gene_variant			XP_016873266.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTNR1B	ENST00000528076.1	c.319G>C	p.Ala107Pro	missense_variant	2/2	3		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

GnomAD3 exomes AF: 0.602 AC: 76807 AN: 127482 Hom.: 24030 AF XY: 0.601 AC XY: 41927 AN XY: 69782

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 SAS exome AF: 0.685

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

Gnomad4 AFR exome AF: 0.518

Gnomad4 AMR exome AF: 0.747

Gnomad4 ASJ exome AF: 0.432

Gnomad4 EAS exome AF: 0.684

Gnomad4 SAS exome AF: 0.682

Gnomad4 FIN exome AF: 0.581

Gnomad4 NFE exome AF: 0.519

Gnomad4 OTH exome AF: 0.553

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

Gnomad4 AFR AF: 0.522

Gnomad4 AMR AF: 0.653

Gnomad4 ASJ AF: 0.440

Gnomad4 EAS AF: 0.695

Gnomad4 SAS AF: 0.687

Gnomad4 FIN AF: 0.575

Gnomad4 NFE AF: 0.516

Gnomad4 OTH AF: 0.535

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 v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1447350; hg19: chr11-92718127;