rs12792653

Positions:

• chr11-92982750-G-A

Variant summary

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

The NM_005959.5(MTNR1B):​c.*438G>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 0.55 in 204,720 control chromosomes in the GnomAD database, including 31,883 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 (23744 hom., cov: 31)
  • Exomes 𝑓: 0.54 (8139 hom.)
• Consequence: MTNR1B NM_005959.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.161

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTNR1B	NM_005959.5	c.*438G>A		3_prime_UTR_variant	2/2	ENST00000257068.3	NP_005950.1
MTNR1B	XM_011542839.3	c.*411+27G>A		intron_variant			XP_011541141.1
MTNR1B	XM_017017777.2	c.*411+27G>A		intron_variant			XP_016873266.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTNR1B	ENST00000257068.3	c.*438G>A		3_prime_UTR_variant	2/2	1	NM_005959.5	ENSP00000257068.2
MTNR1B	ENST00000528076.1	c.165-2057G>A		intron_variant		3		ENSP00000433573.1

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84199 AN: 151758 Hom.: 23704 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: 0.694

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.512

Gnomad OTH AF: 0.540

GnomAD4 exome AF: 0.537 AC: 28386 AN: 52844 Hom.: 8139 Cov.: 0 AF XY: 0.546 AC XY: 14609 AN XY: 26778

Gnomad4 AFR exome AF: 0.535

Gnomad4 AMR exome AF: 0.701

Gnomad4 ASJ exome AF: 0.407

Gnomad4 EAS exome AF: 0.663

Gnomad4 SAS exome AF: 0.687

Gnomad4 FIN exome AF: 0.552

Gnomad4 NFE exome AF: 0.493

Gnomad4 OTH exome AF: 0.512

GnomAD4 genome AF: 0.555 AC: 84302 AN: 151876 Hom.: 23744 Cov.: 31 AF XY: 0.563 AC XY: 41808 AN XY: 74224

Gnomad4 AFR AF: 0.557

Gnomad4 AMR AF: 0.656

Gnomad4 ASJ AF: 0.438

Gnomad4 EAS AF: 0.697

Gnomad4 SAS AF: 0.694

Gnomad4 FIN AF: 0.573

Gnomad4 NFE AF: 0.512

Gnomad4 OTH AF: 0.540

Alfa AF: 0.522 Hom.: 4240

Bravo AF: 0.562

Asia WGS AF: 0.649 AC: 2255 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.9
DANN	Benign	0.83

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

LitVar

Other links and lift over

dbSNP: rs12792653; hg19: chr11-92715916;