rs10765576

Variant names:

• chr11-92973778-A-G
• rs10765576
• NM_005959.5:c.223+3830A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-92973778-A-G
• chr11-92973778-A-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+3830A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 152,016 control chromosomes in the GnomAD database, including 25,262 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 0.57 (25262 hom., cov: 32)
• Consequence: MTNR1B NM_005959.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0800
• Publications: 17 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.69 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+3830A>G		intron	N/A	NP_005950.1	P49286

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTNR1B	ENST00000257068.3	TSL:1 MANE Select	c.223+3830A>G		intron	N/A	ENSP00000257068.2	P49286
	MTNR1B	ENST00000528076.1	TSL:3	c.164+3830A>G		intron	N/A	ENSP00000433573.1	H0YDG4
	MTNR1B	ENST00000532482.1	TSL:5	n.*114+1187A>G		intron	N/A	ENSP00000436101.1	E9PR36

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86905 AN: 151898 Hom.: 25250 Cov.: 32

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.690

Gnomad AMR AF: 0.673

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.691

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.565

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

GnomAD4 genome AF: 0.572 AC: 86966 AN: 152016 Hom.: 25262 Cov.: 32 AF XY: 0.580 AC XY: 43073 AN XY: 74294

African (AFR) AF: 0.509 AC: 21091 AN: 41442

American (AMR) AF: 0.674 AC: 10296 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1592 AN: 3468

East Asian (EAS) AF: 0.709 AC: 3662 AN: 5164

South Asian (SAS) AF: 0.691 AC: 3332 AN: 4822

European-Finnish (FIN) AF: 0.633 AC: 6690 AN: 10572

Middle Eastern (MID) AF: 0.572 AC: 167 AN: 292

European-Non Finnish (NFE) AF: 0.564 AC: 38315 AN: 67948

Other (OTH) AF: 0.565 AC: 1192 AN: 2110

Alfa AF: 0.577 Hom.: 5366

Bravo AF: 0.573

Asia WGS AF: 0.641 AC: 2231 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.3
DANN	Benign	0.46
PhyloP100		0.080
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: rs10765576; hg19: chr11-92706944;