rs12804291

Variant names:

• chr11-92972141-C-T
• rs12804291
• NM_005959.5:c.223+2193C>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.223+2193C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,188 control chromosomes in the GnomAD database, including 2,076 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 0.14 (2076 hom., cov: 32)
• Consequence: MTNR1B NM_005959.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.217
• Publications: 11 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTNR1B	NM_005959.5	c.223+2193C>T		intron_variant	Intron 1 of 1	ENST00000257068.3	NP_005950.1
MTNR1B	XM_011542839.3	c.223+2193C>T		intron_variant	Intron 1 of 2		XP_011541141.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTNR1B	ENST00000257068.3	c.223+2193C>T		intron_variant	Intron 1 of 1	1	NM_005959.5	ENSP00000257068.2
MTNR1B	ENST00000528076.1	c.164+2193C>T		intron_variant	Intron 1 of 1	3		ENSP00000433573.1
MTNR1B	ENST00000532482.1	n.224-320C>T		intron_variant	Intron 1 of 2	5		ENSP00000436101.1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20993 AN: 152070 Hom.: 2074 Cov.: 32

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.0744

Gnomad ASJ AF: 0.0427

Gnomad EAS AF: 0.00481

Gnomad SAS AF: 0.0968

Gnomad FIN AF: 0.0642

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.114

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

GnomAD4 genome AF: 0.138 AC: 21012 AN: 152188 Hom.: 2076 Cov.: 32 AF XY: 0.133 AC XY: 9872 AN XY: 74410

African (AFR) AF: 0.271 AC: 11221 AN: 41472

American (AMR) AF: 0.0743 AC: 1137 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0427 AC: 148 AN: 3470

East Asian (EAS) AF: 0.00482 AC: 25 AN: 5190

South Asian (SAS) AF: 0.0967 AC: 466 AN: 4818

European-Finnish (FIN) AF: 0.0642 AC: 681 AN: 10608

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 6988 AN: 68008

Other (OTH) AF: 0.113 AC: 239 AN: 2110

Alfa AF: 0.114 Hom.: 547

Bravo AF: 0.145

Asia WGS AF: 0.0620 AC: 217 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.9
DANN	Benign	0.67
PhyloP100		0.22
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: rs12804291; hg19: chr11-92705307;