11-92971992-A-G

Variant names:

• chr11-92971992-A-G
• rs4601728
• NM_005959.5:c.223+2044A>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+2044A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,218 control chromosomes in the GnomAD database, including 2,700 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 0.15 (2700 hom., cov: 32)
• Consequence: MTNR1B NM_005959.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• Publications: 12 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.316 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.223+2044A>G		intron	N/A	NP_005950.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTNR1B	ENST00000257068.3	TSL:1 MANE Select	c.223+2044A>G		intron	N/A	ENSP00000257068.2
	MTNR1B	ENST00000528076.1	TSL:3	c.164+2044A>G		intron	N/A	ENSP00000433573.1
	MTNR1B	ENST00000532482.1	TSL:5	n.224-469A>G		intron	N/A	ENSP00000436101.1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23264 AN: 152100 Hom.: 2695 Cov.: 32

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.0787

Gnomad ASJ AF: 0.0606

Gnomad EAS AF: 0.00462

Gnomad SAS AF: 0.0972

Gnomad FIN AF: 0.0643

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.153 AC: 23298 AN: 152218 Hom.: 2700 Cov.: 32 AF XY: 0.147 AC XY: 10941 AN XY: 74422

African (AFR) AF: 0.320 AC: 13302 AN: 41506

American (AMR) AF: 0.0785 AC: 1201 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0606 AC: 210 AN: 3468

East Asian (EAS) AF: 0.00463 AC: 24 AN: 5182

South Asian (SAS) AF: 0.0969 AC: 467 AN: 4820

European-Finnish (FIN) AF: 0.0643 AC: 682 AN: 10610

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

European-Non Finnish (NFE) AF: 0.104 AC: 7041 AN: 68014

Other (OTH) AF: 0.125 AC: 264 AN: 2112

Alfa AF: 0.115 Hom.: 2700

Bravo AF: 0.162

Asia WGS AF: 0.0660 AC: 232 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.0
DANN	Benign	0.64
PhyloP100		1.0
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: rs4601728; hg19: chr11-92705158;