11-92981429-C-T

Variant names:

• chr11-92981429-C-T
• rs6483210
• NM_005959.5:c.224-18C>T

Variant summary

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

The NM_005959.5(MTNR1B):​c.224-18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0376 in 1,605,448 control chromosomes in the GnomAD database, including 2,975 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 0.086 (1214 hom., cov: 32)
  • Exomes 𝑓: 0.032 (1761 hom.)
• Consequence: MTNR1B NM_005959.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.157
• Publications: 5 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.23 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTNR1B	NM_005959.5	MANE Select	c.224-18C>T		intron	N/A	NP_005950.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTNR1B	ENST00000257068.3	TSL:1 MANE Select	c.224-18C>T		intron	N/A	ENSP00000257068.2
	MTNR1B	ENST00000528076.1	TSL:3	c.165-3378C>T		intron	N/A	ENSP00000433573.1
	MTNR1B	ENST00000532482.1	TSL:5	n.*115-18C>T		intron	N/A	ENSP00000436101.1

Frequencies

GnomAD3 genomes AF: 0.0862 AC: 13102 AN: 152020 Hom.: 1212 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.0371

Gnomad ASJ AF: 0.0812

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0119

Gnomad FIN AF: 0.0273

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0295

Gnomad OTH AF: 0.0736

GnomAD2 exomes AF: 0.0395 AC: 9727 AN: 246318 AF XY: 0.0351

Gnomad AFR exome AF: 0.234

Gnomad AMR exome AF: 0.0203

Gnomad ASJ exome AF: 0.0771

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0289

Gnomad NFE exome AF: 0.0296

Gnomad OTH exome AF: 0.0321

GnomAD4 exome AF: 0.0325 AC: 47228 AN: 1453310 Hom.: 1761 Cov.: 31 AF XY: 0.0314 AC XY: 22635 AN XY: 721894

African (AFR) AF: 0.248 AC: 8253 AN: 33272

American (AMR) AF: 0.0228 AC: 1011 AN: 44368

Ashkenazi Jewish (ASJ) AF: 0.0779 AC: 1993 AN: 25598

East Asian (EAS) AF: 0.000152 AC: 6 AN: 39524

South Asian (SAS) AF: 0.0135 AC: 1153 AN: 85400

European-Finnish (FIN) AF: 0.0258 AC: 1350 AN: 52378

Middle Eastern (MID) AF: 0.0563 AC: 322 AN: 5724

European-Non Finnish (NFE) AF: 0.0277 AC: 30620 AN: 1106998

Other (OTH) AF: 0.0420 AC: 2520 AN: 60048

GnomAD4 genome AF: 0.0863 AC: 13122 AN: 152138 Hom.: 1214 Cov.: 32 AF XY: 0.0834 AC XY: 6201 AN XY: 74380

African (AFR) AF: 0.234 AC: 9689 AN: 41456

American (AMR) AF: 0.0370 AC: 566 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0812 AC: 282 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.0119 AC: 57 AN: 4802

European-Finnish (FIN) AF: 0.0273 AC: 290 AN: 10606

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0294 AC: 2002 AN: 68012

Other (OTH) AF: 0.0728 AC: 154 AN: 2114

Alfa AF: 0.0490 Hom.: 1193

Bravo AF: 0.0944

Asia WGS AF: 0.0200 AC: 70 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.95
DANN	Benign	0.77
PhyloP100		-0.16
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: rs6483210; hg19: chr11-92714595; COSMIC: COSV57069840;