rs2119882

Variant names:

• chr4-186555751-T-C
• rs2119882
• NM_005958.4:c.-386A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005958.4(MTNR1A):​c.-386A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 152,118 control chromosomes in the GnomAD database, including 24,791 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 0.56 (24791 hom., cov: 33)
• Consequence: MTNR1A NM_005958.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.870
• Publications: 36 publications found

Genes affected

MTNR1A (HGNC:7463): (melatonin receptor 1A) This gene encodes one of two high affinity forms of a receptor for melatonin, the primary hormone secreted by the pineal gland. This receptor is a G-protein coupled, 7-transmembrane receptor that is responsible for melatonin effects on mammalian circadian rhythm and reproductive alterations affected by day length. The receptor is an integral membrane protein that is readily detectable and localized to two specific regions of the brain. The hypothalamic suprachiasmatic nucleus appears to be involved in circadian rhythm while the hypophysial pars tuberalis may be responsible for the reproductive 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTNR1A	NM_005958.4	c.-386A>G		upstream_gene_variant		ENST00000307161.5	NP_005949.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTNR1A	ENST00000307161.5	c.-386A>G		upstream_gene_variant		1	NM_005958.4	ENSP00000302811.5
MTNR1A	ENST00000703170.1	c.-386A>G		upstream_gene_variant				ENSP00000515216.1

Frequencies

GnomAD3 genomes AF: 0.563 AC: 85624 AN: 152002 Hom.: 24786 Cov.: 33

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.552

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.634

Gnomad OTH AF: 0.571

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

GnomAD4 genome AF: 0.563 AC: 85667 AN: 152118 Hom.: 24791 Cov.: 33 AF XY: 0.560 AC XY: 41675 AN XY: 74360

African (AFR) AF: 0.472 AC: 19609 AN: 41538

American (AMR) AF: 0.552 AC: 8438 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1693 AN: 3470

East Asian (EAS) AF: 0.385 AC: 1980 AN: 5146

South Asian (SAS) AF: 0.401 AC: 1933 AN: 4822

European-Finnish (FIN) AF: 0.657 AC: 6942 AN: 10574

Middle Eastern (MID) AF: 0.562 AC: 164 AN: 292

European-Non Finnish (NFE) AF: 0.634 AC: 43079 AN: 67960

Other (OTH) AF: 0.573 AC: 1211 AN: 2112

Alfa AF: 0.603 Hom.: 5761

Bravo AF: 0.552

Asia WGS AF: 0.419 AC: 1454 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.5
DANN	Benign	0.72
PhyloP100		0.87
PromoterAI		0.0044	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2119882; hg19: chr4-187476905;