chr4-186540475-A-T

Position:

• chr4-186540475-A-T

Variant summary

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

The NM_005958.4(MTNR1A):​c.185-5918T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 152,188 control chromosomes in the GnomAD database, including 32,130 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 0.64 (32130 hom., cov: 35)
• Consequence: MTNR1A NM_005958.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.218

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTNR1A	NM_005958.4	c.185-5918T>A		intron_variant		ENST00000307161.5	NP_005949.1
LOC105377596	XR_007058498.1	n.144-5169A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTNR1A	ENST00000307161.5	c.185-5918T>A		intron_variant		1	NM_005958.4	ENSP00000302811.5
ENSG00000272297	ENST00000509111.2	c.145+14707T>A		intron_variant		3		ENSP00000422449.2
MTNR1A	ENST00000703170.1	c.185-5918T>A		intron_variant				ENSP00000515216.1

Frequencies

GnomAD3 genomes AF: 0.639 AC: 97205 AN: 152070 Hom.: 32124 Cov.: 35

Gnomad AFR AF: 0.535

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.622

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.407

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.732

Gnomad OTH AF: 0.666

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

GnomAD4 genome AF: 0.639 AC: 97250 AN: 152188 Hom.: 32130 Cov.: 35 AF XY: 0.632 AC XY: 47037 AN XY: 74380

Gnomad4 AFR AF: 0.535

Gnomad4 AMR AF: 0.639

Gnomad4 ASJ AF: 0.622

Gnomad4 EAS AF: 0.347

Gnomad4 SAS AF: 0.407

Gnomad4 FIN AF: 0.706

Gnomad4 NFE AF: 0.732

Gnomad4 OTH AF: 0.667

Alfa AF: 0.685 Hom.: 4270

Bravo AF: 0.631

Asia WGS AF: 0.420 AC: 1458 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.1
DANN	Benign	0.69

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: rs2165667; hg19: chr4-187461629;