rs1447351

Positions:

• chr11-92984997-A-G
• chr11-92984997-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000528076.1(MTNR1B):​c.*16A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 451,308 control chromosomes in the GnomAD database, including 75,820 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 (23976 hom., cov: 33)
  • Exomes 𝑓: 0.58 (51844 hom.)
• Consequence: MTNR1B ENST00000528076.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.142

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=-0.76).
• 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			downstream_gene_variant			XP_011541141.1
MTNR1B	XM_017017777.2			downstream_gene_variant			XP_016873266.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTNR1B	ENST00000528076.1	c.*16A>G		3_prime_UTR_variant	2/2	3		ENSP00000433573

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84639 AN: 151924 Hom.: 23944 Cov.: 33

Gnomad AFR AF: 0.558

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.656

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.583

Gnomad NFE AF: 0.516

Gnomad OTH AF: 0.543

GnomAD3 exomes AF: 0.607 AC: 75236 AN: 124000 Hom.: 23612 AF XY: 0.604 AC XY: 40966 AN XY: 67814

Gnomad AFR exome AF: 0.554

Gnomad AMR exome AF: 0.750

Gnomad ASJ exome AF: 0.436

Gnomad EAS exome AF: 0.684

Gnomad SAS exome AF: 0.686

Gnomad FIN exome AF: 0.587

Gnomad NFE exome AF: 0.518

Gnomad OTH exome AF: 0.566

GnomAD4 exome AF: 0.579 AC: 173359 AN: 299268 Hom.: 51844 Cov.: 0 AF XY: 0.587 AC XY: 100100 AN XY: 170548

Gnomad4 AFR exome AF: 0.557

Gnomad4 AMR exome AF: 0.748

Gnomad4 ASJ exome AF: 0.433

Gnomad4 EAS exome AF: 0.685

Gnomad4 SAS exome AF: 0.681

Gnomad4 FIN exome AF: 0.580

Gnomad4 NFE exome AF: 0.519

Gnomad4 OTH exome AF: 0.555

GnomAD4 genome AF: 0.557 AC: 84733 AN: 152040 Hom.: 23976 Cov.: 33 AF XY: 0.565 AC XY: 41996 AN XY: 74300

Gnomad4 AFR AF: 0.559

Gnomad4 AMR AF: 0.657

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.695

Gnomad4 SAS AF: 0.684

Gnomad4 FIN AF: 0.575

Gnomad4 NFE AF: 0.516

Gnomad4 OTH AF: 0.543

Alfa AF: 0.525 Hom.: 4612

Bravo AF: 0.565

Asia WGS AF: 0.646 AC: 2245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.6
DANN	Benign	0.88

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1447351; hg19: chr11-92718163;