4-186544837-A-G

Variant names:

• chr4-186544837-A-G
• rs13113549
• NM_005958.4:c.185-10280T>C

Variant summary

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

The NM_005958.4(MTNR1A):​c.185-10280T>C 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 151,952 control chromosomes in the GnomAD database, including 13,191 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 (13191 hom., cov: 32)
• Consequence: MTNR1A NM_005958.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.897
• Publications: 8 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=-0.91).
• 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 rank	MANE	Protein	UniProt
MTNR1A	NM_005958.4	c.185-10280T>C		intron_variant	Intron 1 of 1	ENST00000307161.5	NP_005949.1
LOC105377596	XR_007058498.1	n.144-807A>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTNR1A	ENST00000307161.5	c.185-10280T>C		intron_variant	Intron 1 of 1	1	NM_005958.4	ENSP00000302811.5
ENSG00000272297	ENST00000509111.2	c.145+10345T>C		intron_variant	Intron 1 of 1	3		ENSP00000422449.2

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62684 AN: 151834 Hom.: 13184 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: 0.402

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.382

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: 62735 AN: 151952 Hom.: 13191 Cov.: 32 AF XY: 0.417 AC XY: 30974 AN XY: 74264

African (AFR) AF: 0.415 AC: 17186 AN: 41416

American (AMR) AF: 0.433 AC: 6619 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1592 AN: 3470

East Asian (EAS) AF: 0.615 AC: 3169 AN: 5156

South Asian (SAS) AF: 0.555 AC: 2666 AN: 4806

European-Finnish (FIN) AF: 0.402 AC: 4232 AN: 10538

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.382 AC: 25932 AN: 67964

Other (OTH) AF: 0.397 AC: 837 AN: 2110

Alfa AF: 0.394 Hom.: 46516

Bravo AF: 0.417

Asia WGS AF: 0.547 AC: 1903 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	0.61
DANN	Benign	0.53
PhyloP100		-0.90
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: rs13113549; hg19: chr4-187465991;