4-186540490-T-C

Variant names:

• chr4-186540490-T-C
• rs6847693
• NM_005958.4:c.185-5933A>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.185-5933A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,292 control chromosomes in the GnomAD database, including 3,428 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 0.19 (3428 hom., cov: 36)
• Consequence: MTNR1A NM_005958.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.195
• Publications: 12 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.55 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTNR1A	NM_005958.4	MANE Select	c.185-5933A>G		intron	N/A	NP_005949.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTNR1A	ENST00000307161.5	TSL:1 MANE Select	c.185-5933A>G		intron	N/A	ENSP00000302811.5
	ENSG00000272297	ENST00000509111.2	TSL:3	c.145+14692A>G		intron	N/A	ENSP00000422449.2
	MTNR1A	ENST00000703170.1		c.185-5933A>G		intron	N/A	ENSP00000515216.1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29021 AN: 152174 Hom.: 3431 Cov.: 36

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.152

Gnomad EAS AF: 0.567

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.191 AC: 29032 AN: 152292 Hom.: 3428 Cov.: 36 AF XY: 0.198 AC XY: 14752 AN XY: 74462

African (AFR) AF: 0.153 AC: 6360 AN: 41564

American (AMR) AF: 0.239 AC: 3655 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.152 AC: 529 AN: 3472

East Asian (EAS) AF: 0.567 AC: 2932 AN: 5174

South Asian (SAS) AF: 0.437 AC: 2111 AN: 4828

European-Finnish (FIN) AF: 0.180 AC: 1915 AN: 10616

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10839 AN: 68012

Other (OTH) AF: 0.166 AC: 352 AN: 2116

Alfa AF: 0.175 Hom.: 2045

Bravo AF: 0.193

Asia WGS AF: 0.446 AC: 1549 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.4
DANN	Benign	0.71
PhyloP100		0.20
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: rs6847693; hg19: chr4-187461644;