ENST00000528076.1:c.*16A>G

Variant names:

• chr11-92984997-A-G
• rs1447351
• ENST00000528076.1:c.*16A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 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=-0.76).
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTNR1B	ENST00000528076.1	TSL:3	c.*16A>G		3_prime_UTR	Exon 2 of 2	ENSP00000433573.1	H0YDG4

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

GnomAD2 exomes AF: 0.607 AC: 75236 AN: 124000 AF XY: 0.604

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 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

African (AFR) AF: 0.557 AC: 4717 AN: 8476

American (AMR) AF: 0.748 AC: 20154 AN: 26928

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 4487 AN: 10370

East Asian (EAS) AF: 0.685 AC: 6294 AN: 9186

South Asian (SAS) AF: 0.681 AC: 40016 AN: 58738

European-Finnish (FIN) AF: 0.580 AC: 7068 AN: 12182

Middle Eastern (MID) AF: 0.560 AC: 1532 AN: 2738

European-Non Finnish (NFE) AF: 0.519 AC: 81316 AN: 156640

Other (OTH) AF: 0.555 AC: 7775 AN: 14010

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

African (AFR) AF: 0.559 AC: 23172 AN: 41470

American (AMR) AF: 0.657 AC: 10042 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1525 AN: 3472

East Asian (EAS) AF: 0.695 AC: 3579 AN: 5146

South Asian (SAS) AF: 0.684 AC: 3299 AN: 4820

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

Middle Eastern (MID) AF: 0.586 AC: 171 AN: 292

European-Non Finnish (NFE) AF: 0.516 AC: 35101 AN: 67974

Other (OTH) AF: 0.543 AC: 1143 AN: 2106

Alfa AF: 0.526 Hom.: 4742

Bravo AF: 0.565

Asia WGS AF: 0.646 AC: 2245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.6
DANN	Benign	0.88
PhyloP100		-0.14

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1447351;

hg19: chr11-92718163;