4-186530387-G-C

Position:

• chr4-186530387-G-C

Variant summary

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

The ENST00000509111.2(ENSG00000272297):​c.145+24795C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.731 in 152,170 control chromosomes in the GnomAD database, including 41,633 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 0.73 (41633 hom., cov: 32)
• Consequence: ENSG00000272297 ENST00000509111.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.203

Genes affected

ENSG00000272297 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC105377596	XR_007058498.1	n.143+5492G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000272297	ENST00000509111.2	c.145+24795C>G		intron_variant		3		ENSP00000422449.2
MTNR1A	ENST00000703170	c.*3302C>G		3_prime_UTR_variant	2/2			ENSP00000515216.1

Frequencies

GnomAD3 genomes AF: 0.731 AC: 111183 AN: 152052 Hom.: 41629 Cov.: 32

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.807

Gnomad AMR AF: 0.814

Gnomad ASJ AF: 0.665

Gnomad EAS AF: 0.922

Gnomad SAS AF: 0.846

Gnomad FIN AF: 0.784

Gnomad MID AF: 0.790

Gnomad NFE AF: 0.792

Gnomad OTH AF: 0.740

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

GnomAD4 genome AF: 0.731 AC: 111225 AN: 152170 Hom.: 41633 Cov.: 32 AF XY: 0.734 AC XY: 54599 AN XY: 74392

Gnomad4 AFR AF: 0.553

Gnomad4 AMR AF: 0.814

Gnomad4 ASJ AF: 0.665

Gnomad4 EAS AF: 0.921

Gnomad4 SAS AF: 0.844

Gnomad4 FIN AF: 0.784

Gnomad4 NFE AF: 0.792

Gnomad4 OTH AF: 0.743

Alfa AF: 0.758 Hom.: 5505

Bravo AF: 0.725

Asia WGS AF: 0.868 AC: 3018 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.2
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs6838290; hg19: chr4-187451541;