11-92975633-C-G

Variant names:

• chr11-92975633-C-G
• rs12272268
• NM_005959.5:c.223+5685C>G

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+5685C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0924 in 152,218 control chromosomes in the GnomAD database, including 1,461 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 0.092 (1461 hom., cov: 33)
• Consequence: MTNR1B NM_005959.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0250
• Publications: 4 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTNR1B	NM_005959.5	c.223+5685C>G		intron_variant	Intron 1 of 1	ENST00000257068.3	NP_005950.1
MTNR1B	XM_011542839.3	c.223+5685C>G		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+5685C>G		intron_variant	Intron 1 of 1	1	NM_005959.5	ENSP00000257068.2
MTNR1B	ENST00000528076.1	c.164+5685C>G		intron_variant	Intron 1 of 1	3		ENSP00000433573.1
MTNR1B	ENST00000532482.1	n.*114+3042C>G		intron_variant	Intron 2 of 2	5		ENSP00000436101.1

Frequencies

GnomAD3 genomes AF: 0.0923 AC: 14044 AN: 152100 Hom.: 1459 Cov.: 33

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.0403

Gnomad ASJ AF: 0.0813

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0118

Gnomad FIN AF: 0.0273

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0298

Gnomad OTH AF: 0.0774

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

GnomAD4 genome AF: 0.0924 AC: 14069 AN: 152218 Hom.: 1461 Cov.: 33 AF XY: 0.0889 AC XY: 6617 AN XY: 74420

African (AFR) AF: 0.255 AC: 10556 AN: 41476

American (AMR) AF: 0.0402 AC: 616 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0813 AC: 282 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.0118 AC: 57 AN: 4824

European-Finnish (FIN) AF: 0.0273 AC: 290 AN: 10620

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0297 AC: 2023 AN: 68026

Other (OTH) AF: 0.0766 AC: 162 AN: 2116

Alfa AF: 0.0686 Hom.: 129

Bravo AF: 0.102

Asia WGS AF: 0.0210 AC: 73 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.6
DANN	Benign	0.26
PhyloP100		-0.025
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: rs12272268; hg19: chr11-92708799;