rs13140012

Variant names:

• chr4-186544404-T-A
• rs13140012
• NM_005958.4:c.185-9847A>T

Your query was ambiguous. Multiple possible variants found:

• chr4-186544404-T-A
• chr4-186544404-T-C
• chr4-186544404-T-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.185-9847A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 152,048 control chromosomes in the GnomAD database, including 13,207 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 0.41 (13207 hom., cov: 32)
• Consequence: MTNR1A NM_005958.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.289
• Publications: 17 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.6 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.185-9847A>T		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.185-9847A>T		intron	N/A	ENSP00000302811.5
	ENSG00000272297	ENST00000509111.2	TSL:3	c.145+10778A>T		intron	N/A	ENSP00000422449.2
	MTNR1A	ENST00000703170.1		c.185-9847A>T		intron	N/A	ENSP00000515216.1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62757 AN: 151928 Hom.: 13202 Cov.: 32

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.413 AC: 62805 AN: 152048 Hom.: 13207 Cov.: 32 AF XY: 0.417 AC XY: 30991 AN XY: 74300

African (AFR) AF: 0.416 AC: 17241 AN: 41470

American (AMR) AF: 0.433 AC: 6607 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.458 AC: 1590 AN: 3468

East Asian (EAS) AF: 0.618 AC: 3183 AN: 5150

South Asian (SAS) AF: 0.555 AC: 2671 AN: 4810

European-Finnish (FIN) AF: 0.401 AC: 4239 AN: 10572

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.382 AC: 25940 AN: 67984

Other (OTH) AF: 0.395 AC: 836 AN: 2114

Alfa AF: 0.233 Hom.: 503

Bravo AF: 0.417

Asia WGS AF: 0.546 AC: 1899 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.3
DANN	Benign	0.27
PhyloP100		0.29
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: rs13140012; hg19: chr4-187465558;