rs6553010

Variant names:

• chr4-186535189-G-A
• rs6553010
• NM_005958.4:c.185-632C>T

Your query was ambiguous. Multiple possible variants found:

• chr4-186535189-G-A
• chr4-186535189-G-C
• chr4-186535189-G-T

Variant summary

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

The NM_005958.4(MTNR1A):​c.185-632C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,000 control chromosomes in the GnomAD database, including 4,891 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 0.24 (4891 hom., cov: 32)
• Consequence: MTNR1A NM_005958.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.218
• Publications: 19 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.618 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTNR1A	NM_005958.4	c.185-632C>T		intron_variant	Intron 1 of 1	ENST00000307161.5	NP_005949.1
MTNR1A	XM_011532002.4	c.-71-632C>T		intron_variant	Intron 1 of 1		XP_011530304.1
LOC105377596	XR_007058498.1	n.143+10294G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTNR1A	ENST00000307161.5	c.185-632C>T		intron_variant	Intron 1 of 1	1	NM_005958.4	ENSP00000302811.5
ENSG00000272297	ENST00000509111.2	c.145+19993C>T		intron_variant	Intron 1 of 1	3		ENSP00000422449.2

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35850 AN: 151882 Hom.: 4893 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.272

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.236 AC: 35867 AN: 152000 Hom.: 4891 Cov.: 32 AF XY: 0.241 AC XY: 17917 AN XY: 74298

African (AFR) AF: 0.219 AC: 9089 AN: 41488

American (AMR) AF: 0.273 AC: 4167 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 603 AN: 3468

East Asian (EAS) AF: 0.637 AC: 3271 AN: 5138

South Asian (SAS) AF: 0.471 AC: 2266 AN: 4814

European-Finnish (FIN) AF: 0.187 AC: 1972 AN: 10570

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13685 AN: 67960

Other (OTH) AF: 0.208 AC: 439 AN: 2106

Alfa AF: 0.206 Hom.: 5782

Bravo AF: 0.242

Asia WGS AF: 0.505 AC: 1752 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.98
DANN	Benign	0.57
PhyloP100		-0.22
Mutation Taster		=100/0	polymorphism (auto)

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: rs6553010; hg19: chr4-187456343;