chr11-92981951-A-G

Variant names:

• chr11-92981951-A-G
• rs61747139
• NM_005959.5:c.728A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The ENST00000257068.3(MTNR1B):​c.728A>G​(p.Lys243Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0377 in 1,614,164 control chromosomes in the GnomAD database, including 2,997 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.087 (1227 hom., cov: 33)
  • Exomes 𝑓: 0.033 (1770 hom.)
• Consequence: MTNR1B ENST00000257068.3 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.170
• Publications: 19 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00430429).
• BP6: Variant 11-92981951-A-G is Benign according to our data. Variant chr11-92981951-A-G is described in ClinVar as Benign. ClinVar VariationId is 3060517.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000257068.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTNR1B	NM_005959.5	MANE Select	c.728A>G	p.Lys243Arg	missense	Exon 2 of 2	NP_005950.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTNR1B	ENST00000257068.3	TSL:1 MANE Select	c.728A>G	p.Lys243Arg	missense	Exon 2 of 2	ENSP00000257068.2
	MTNR1B	ENST00000532482.1	TSL:5	n.*619A>G		non_coding_transcript_exon	Exon 3 of 3	ENSP00000436101.1
	MTNR1B	ENST00000532482.1	TSL:5	n.*619A>G		3_prime_UTR	Exon 3 of 3	ENSP00000436101.1

Frequencies

GnomAD3 genomes AF: 0.0865 AC: 13168 AN: 152160 Hom.: 1225 Cov.: 33

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.0376

Gnomad ASJ AF: 0.0801

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0118

Gnomad FIN AF: 0.0272

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0297

Gnomad OTH AF: 0.0736

GnomAD2 exomes AF: 0.0395 AC: 9930 AN: 251458 AF XY: 0.0351

Gnomad AFR exome AF: 0.235

Gnomad AMR exome AF: 0.0206

Gnomad ASJ exome AF: 0.0762

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0292

Gnomad NFE exome AF: 0.0297

Gnomad OTH exome AF: 0.0327

GnomAD4 exome AF: 0.0326 AC: 47627 AN: 1461886 Hom.: 1770 Cov.: 31 AF XY: 0.0314 AC XY: 22853 AN XY: 727244

African (AFR) AF: 0.249 AC: 8324 AN: 33480

American (AMR) AF: 0.0229 AC: 1024 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0766 AC: 2003 AN: 26136

East Asian (EAS) AF: 0.000151 AC: 6 AN: 39698

South Asian (SAS) AF: 0.0135 AC: 1164 AN: 86258

European-Finnish (FIN) AF: 0.0259 AC: 1382 AN: 53416

Middle Eastern (MID) AF: 0.0569 AC: 328 AN: 5768

European-Non Finnish (NFE) AF: 0.0278 AC: 30861 AN: 1112010

Other (OTH) AF: 0.0420 AC: 2535 AN: 60396

GnomAD4 genome AF: 0.0866 AC: 13185 AN: 152278 Hom.: 1227 Cov.: 33 AF XY: 0.0836 AC XY: 6226 AN XY: 74472

African (AFR) AF: 0.234 AC: 9734 AN: 41524

American (AMR) AF: 0.0375 AC: 574 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0801 AC: 278 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.0118 AC: 57 AN: 4830

European-Finnish (FIN) AF: 0.0272 AC: 289 AN: 10616

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0296 AC: 2017 AN: 68034

Other (OTH) AF: 0.0728 AC: 154 AN: 2114

Alfa AF: 0.0561 Hom.: 397

Bravo AF: 0.0947

TwinsUK AF: 0.0337 AC: 125

ALSPAC AF: 0.0288 AC: 111

ESP6500AA AF: 0.235 AC: 1033

ESP6500EA AF: 0.0330 AC: 284

ExAC AF: 0.0421 AC: 5116

Asia WGS AF: 0.0190 AC: 67 AN: 3478

EpiCase AF: 0.0347

EpiControl AF: 0.0294

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	MTNR1B-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.6
DANN	Benign	0.88
DEOGEN2	Benign	0.048	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0063	N
LIST_S2	Benign	0.56	T
MetaRNN	Benign	0.0043	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.26	N
PhyloP100		0.17
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.020	N
REVEL	Benign	0.060
Sift	Benign	0.77	T
Sift4G	Benign	0.47	T
Polyphen		0.0010	B
Vest4		0.0030
MPC		0.13
ClinPred		0.000014	T
GERP RS		1.1
Varity_R		0.030
gMVP		0.14
Mutation Taster		=99/1	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: rs61747139; hg19: chr11-92715117;