4-186530387-G-C

Variant names:

• chr4-186530387-G-C
• rs6838290
• ENST00000509111.2:c.145+24795C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000509111.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000272297	ENST00000509111.2	TSL:3	c.145+24795C>G		intron	N/A	ENSP00000422449.2
	MTNR1A	ENST00000703170.1		c.*3302C>G		3_prime_UTR	Exon 2 of 2	ENSP00000515216.1
	ENSG00000300474	ENST00000772138.1		n.735+5492G>C		intron	N/A

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

African (AFR) AF: 0.553 AC: 22933 AN: 41468

American (AMR) AF: 0.814 AC: 12450 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.665 AC: 2309 AN: 3470

East Asian (EAS) AF: 0.921 AC: 4778 AN: 5186

South Asian (SAS) AF: 0.844 AC: 4064 AN: 4816

European-Finnish (FIN) AF: 0.784 AC: 8307 AN: 10602

Middle Eastern (MID) AF: 0.781 AC: 228 AN: 292

European-Non Finnish (NFE) AF: 0.792 AC: 53852 AN: 68020

Other (OTH) AF: 0.743 AC: 1568 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.2
DANN	Benign	0.61
PhyloP100		0.20

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

Other links and lift over

dbSNP: rs6838290; hg19: chr4-187451541;