4-186540552-G-A

Variant names:

• chr4-186540552-G-A
• rs2165666
• NM_005958.4:c.185-5995C>T

Variant summary

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

The NM_005958.4(MTNR1A):​c.185-5995C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 152,134 control chromosomes in the GnomAD database, including 29,161 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 0.60 (29161 hom., cov: 34)
• Consequence: MTNR1A NM_005958.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 16 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]

ENSG00000272297 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTNR1A	NM_005958.4	c.185-5995C>T		intron_variant	Intron 1 of 1	ENST00000307161.5	NP_005949.1
LOC105377596	XR_007058498.1	n.144-5092G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTNR1A	ENST00000307161.5	c.185-5995C>T		intron_variant	Intron 1 of 1	1	NM_005958.4	ENSP00000302811.5
ENSG00000272297	ENST00000509111.2	c.145+14630C>T		intron_variant	Intron 1 of 1	3		ENSP00000422449.2

Frequencies

GnomAD3 genomes AF: 0.599 AC: 90996 AN: 152016 Hom.: 29163 Cov.: 34

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.707

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.731

Gnomad OTH AF: 0.634

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

GnomAD4 genome AF: 0.598 AC: 91019 AN: 152134 Hom.: 29161 Cov.: 34 AF XY: 0.593 AC XY: 44067 AN XY: 74354

African (AFR) AF: 0.394 AC: 16325 AN: 41486

American (AMR) AF: 0.624 AC: 9536 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 2151 AN: 3468

East Asian (EAS) AF: 0.346 AC: 1790 AN: 5168

South Asian (SAS) AF: 0.406 AC: 1959 AN: 4822

European-Finnish (FIN) AF: 0.707 AC: 7490 AN: 10590

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.732 AC: 49738 AN: 67992

Other (OTH) AF: 0.636 AC: 1345 AN: 2116

Alfa AF: 0.684 Hom.: 157845

Bravo AF: 0.584

Asia WGS AF: 0.409 AC: 1422 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.99
DANN	Benign	0.71
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: rs2165666; hg19: chr4-187461706;