rs3781637

Variant names:

• chr11-92980604-T-C
• rs3781637
• NM_005959.5:c.224-843T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005959.5(MTNR1B):​c.224-843T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0203 in 152,272 control chromosomes in the GnomAD database, including 91 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 0.020 (91 hom., cov: 33)
• Consequence: MTNR1B NM_005959.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.66
• Publications: 10 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.133 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005959.5. 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
	MTNR1B	NM_005959.5	MANE Select	c.224-843T>C		intron	N/A	NP_005950.1	P49286

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTNR1B	ENST00000257068.3	TSL:1 MANE Select	c.224-843T>C		intron	N/A	ENSP00000257068.2	P49286
	MTNR1B	ENST00000528076.1	TSL:3	c.165-4203T>C		intron	N/A	ENSP00000433573.1	H0YDG4
	MTNR1B	ENST00000532482.1	TSL:5	n.*115-843T>C		intron	N/A	ENSP00000436101.1	E9PR36

Frequencies

GnomAD3 genomes AF: 0.0204 AC: 3099 AN: 152154 Hom.: 91 Cov.: 33

Gnomad AFR AF: 0.0134

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0192

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.0670

Gnomad FIN AF: 0.0300

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0117

Gnomad OTH AF: 0.0215

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0203 AC: 3095 AN: 152272 Hom.: 91 Cov.: 33 AF XY: 0.0222 AC XY: 1650 AN XY: 74446

African (AFR) AF: 0.0134 AC: 555 AN: 41566

American (AMR) AF: 0.0192 AC: 293 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0104 AC: 36 AN: 3470

East Asian (EAS) AF: 0.141 AC: 727 AN: 5156

South Asian (SAS) AF: 0.0670 AC: 323 AN: 4820

European-Finnish (FIN) AF: 0.0300 AC: 319 AN: 10620

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0117 AC: 794 AN: 68020

Other (OTH) AF: 0.0203 AC: 43 AN: 2114

Alfa AF: 0.0120 Hom.: 0

Bravo AF: 0.0181

Asia WGS AF: 0.0740 AC: 258 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	0.30
DANN	Benign	0.79
PhyloP100		-3.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3781637; hg19: chr11-92713770;