rs12804291

Positions:

• chr11-92972141-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.89).
• 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/exons	MANE	Protein	UniProt
MTNR1B	NM_005959.5	c.223+2193C>T		intron_variant		ENST00000257068.3	NP_005950.1
MTNR1B	XM_011542839.3	c.223+2193C>T		intron_variant			XP_011541141.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTNR1B	ENST00000257068.3	c.223+2193C>T		intron_variant		1	NM_005959.5	ENSP00000257068	P1
MTNR1B	ENST00000528076.1	c.165+2193C>T		intron_variant		3		ENSP00000433573
MTNR1B	ENST00000532482.1	c.224-320C>T		intron_variant, NMD_transcript_variant		5		ENSP00000436101

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

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.0743

Gnomad4 ASJ AF: 0.0427

Gnomad4 EAS AF: 0.00482

Gnomad4 SAS AF: 0.0967

Gnomad4 FIN AF: 0.0642

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.113

Alfa AF: 0.113 Hom.: 471

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

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: rs12804291; hg19: chr11-92705307;