4-186540490-T-C

Position:

• chr4-186540490-T-C

Variant summary

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

The ENST00000307161.5(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 ENST00000307161.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.195

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTNR1A	NM_005958.4	c.185-5933A>G		intron_variant		ENST00000307161.5	NP_005949.1
LOC105377596	XR_007058498.1	n.144-5154T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTNR1A	ENST00000307161.5	c.185-5933A>G		intron_variant		1	NM_005958.4	ENSP00000302811	P1
MTNR1A	ENST00000703170.1	c.185-5933A>G		intron_variant				ENSP00000515216	P1

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

Gnomad4 AFR AF: 0.153

Gnomad4 AMR AF: 0.239

Gnomad4 ASJ AF: 0.152

Gnomad4 EAS AF: 0.567

Gnomad4 SAS AF: 0.437

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.166

Alfa AF: 0.180 Hom.: 1662

Bravo AF: 0.193

Asia WGS AF: 0.446 AC: 1549 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.4
DANN	Benign	0.71

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: rs6847693; hg19: chr4-187461644;