rs10765576

Positions:

• chr11-92973778-A-G
• chr11-92973778-A-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+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

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTNR1B	NM_005959.5	c.223+3830A>G		intron_variant		ENST00000257068.3	NP_005950.1
MTNR1B	XM_011542839.3	c.223+3830A>G		intron_variant			XP_011541141.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTNR1B	ENST00000257068.3	c.223+3830A>G		intron_variant		1	NM_005959.5	ENSP00000257068	P1
MTNR1B	ENST00000528076.1	c.165+3830A>G		intron_variant		3		ENSP00000433573
MTNR1B	ENST00000532482.1	c.*114+1187A>G		intron_variant, NMD_transcript_variant		5		ENSP00000436101

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

Gnomad4 AFR AF: 0.509

Gnomad4 AMR AF: 0.674

Gnomad4 ASJ AF: 0.459

Gnomad4 EAS AF: 0.709

Gnomad4 SAS AF: 0.691

Gnomad4 FIN AF: 0.633

Gnomad4 NFE AF: 0.564

Gnomad4 OTH AF: 0.565

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.3
DANN	Benign	0.46

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: rs10765576; hg19: chr11-92706944;