4-186550471-T-C

Variant names:

• chr4-186550471-T-C
• rs2375801
• NM_005958.4:c.184+4711A>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.184+4711A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 152,050 control chromosomes in the GnomAD database, including 9,088 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 0.34 (9088 hom., cov: 33)
• Consequence: MTNR1A NM_005958.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15
• Publications: 11 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005958.4. 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
	MTNR1A	NM_005958.4	MANE Select	c.184+4711A>G		intron	N/A	NP_005949.1	P48039

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTNR1A	ENST00000307161.5	TSL:1 MANE Select	c.184+4711A>G		intron	N/A	ENSP00000302811.5	P48039
	ENSG00000272297	ENST00000509111.2	TSL:3	c.145+4711A>G		intron	N/A	ENSP00000422449.2	H0Y8X5
	MTNR1A	ENST00000703170.1		c.184+4711A>G		intron	N/A	ENSP00000515216.1	P48039

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51862 AN: 151932 Hom.: 9091 Cov.: 33

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.550

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.341 AC: 51878 AN: 152050 Hom.: 9088 Cov.: 33 AF XY: 0.345 AC XY: 25653 AN XY: 74316

African (AFR) AF: 0.289 AC: 11999 AN: 41472

American (AMR) AF: 0.371 AC: 5664 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1324 AN: 3470

East Asian (EAS) AF: 0.549 AC: 2835 AN: 5160

South Asian (SAS) AF: 0.492 AC: 2372 AN: 4826

European-Finnish (FIN) AF: 0.352 AC: 3712 AN: 10560

Middle Eastern (MID) AF: 0.329 AC: 96 AN: 292

European-Non Finnish (NFE) AF: 0.337 AC: 22904 AN: 67976

Other (OTH) AF: 0.323 AC: 682 AN: 2110

Alfa AF: 0.343 Hom.: 5499

Bravo AF: 0.342

Asia WGS AF: 0.475 AC: 1650 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.61
PhyloP100		1.2
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: rs2375801; hg19: chr4-187471625;