rs13113915

Positions:

• chr4-186544810-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005958.4(MTNR1A):​c.185-10253C>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 151,966 control chromosomes in the GnomAD database, including 13,180 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 (13180 hom., cov: 32)
• Consequence: MTNR1A NM_005958.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.226

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]

LOC105377596 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTNR1A	NM_005958.4	c.185-10253C>T		intron_variant		ENST00000307161.5	NP_005949.1
LOC105377596	XR_007058498.1	n.144-834G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTNR1A	ENST00000307161.5	c.185-10253C>T		intron_variant		1	NM_005958.4	ENSP00000302811	P1
MTNR1A	ENST00000703170.1	c.185-10253C>T		intron_variant				ENSP00000515216	P1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62672 AN: 151848 Hom.: 13175 Cov.: 32

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.432

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.381

Gnomad OTH AF: 0.399

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

GnomAD4 genome AF: 0.413 AC: 62720 AN: 151966 Hom.: 13180 Cov.: 32 AF XY: 0.417 AC XY: 30970 AN XY: 74288

Gnomad4 AFR AF: 0.415

Gnomad4 AMR AF: 0.433

Gnomad4 ASJ AF: 0.459

Gnomad4 EAS AF: 0.615

Gnomad4 SAS AF: 0.555

Gnomad4 FIN AF: 0.401

Gnomad4 NFE AF: 0.381

Gnomad4 OTH AF: 0.397

Alfa AF: 0.394 Hom.: 2909

Bravo AF: 0.416

Asia WGS AF: 0.546 AC: 1899 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.6
DANN	Benign	0.62

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

Publications

LitVar

Other links and lift over

dbSNP: rs13113915; hg19: chr4-187465964;