Variant 4-186533818-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_005958.4(MTNR1A):c.924A>G(p.Arg308=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0401 in 1,614,016 control chromosomes in the GnomAD database, including 1,612 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 96 hom., cov: 32)

Exomes 𝑓: 0.041 ( 1516 hom. )

Consequence

MTNR1A
NM_005958.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.321

Variant links:

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]

MTNR1A links:

LOC105377596 (HGNC:):

LOC105377596 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 4-186533818-T-C is Benign according to our data. Variant chr4-186533818-T-C is described in ClinVar as [Benign]. Clinvar id is 1250542.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.321 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MTNR1A	NM_005958.4 linkuse as main transcript	c.924A>G	p.Arg308=	synonymous_variant	2/2	ENST00000307161.5	NP_005949.1
LOC105377596	XR_007058498.1 linkuse as main transcript	n.143+8923T>C		intron_variant, non_coding_transcript_variant
MTNR1A	XM_011532002.4 linkuse as main transcript	c.669A>G	p.Arg223=	synonymous_variant	2/2		XP_011530304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTNR1A	ENST00000307161.5 linkuse as main transcript	c.924A>G	p.Arg308=	synonymous_variant	2/2	1	NM_005958.4	ENSP00000302811	P1
MTNR1A	ENST00000703170.1 linkuse as main transcript	c.924A>G	p.Arg308=	synonymous_variant	2/2			ENSP00000515216	P1

Frequencies

GnomAD3 genomes

AF:

0.0293

AC:

4451

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00819

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0290

Gnomad ASJ

AF:

0.0225

Gnomad EAS

AF:

0.0699

Gnomad SAS

AF:

0.0326

Gnomad FIN

AF:

0.00547

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0427

Gnomad OTH

AF:

0.0341

GnomAD3 exomes

AF:

0.0332

AC:

8344

AN:

251494

Hom.:

220

AF XY:

0.0347

AC XY:

4717

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.00726

Gnomad AMR exome

AF:

0.0185

Gnomad ASJ exome

AF:

0.0221

Gnomad EAS exome

AF:

0.0724

Gnomad SAS exome

AF:

0.0326

Gnomad FIN exome

AF:

0.00647

Gnomad NFE exome

AF:

0.0411

Gnomad OTH exome

AF:

0.0358

GnomAD4 exome

AF:

0.0412

AC:

60262

AN:

1461830

Hom.:

1516

Cov.:

AF XY:

0.0413

AC XY:

30038

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.00684

Gnomad4 AMR exome

AF:

0.0203

Gnomad4 ASJ exome

AF:

0.0214

Gnomad4 EAS exome

AF:

0.0697

Gnomad4 SAS exome

AF:

0.0349

Gnomad4 FIN exome

AF:

0.00745

Gnomad4 NFE exome

AF:

0.0445

Gnomad4 OTH exome

AF:

0.0436

GnomAD4 genome

AF:

0.0292

AC:

4446

AN:

152186

Hom.:

Cov.:

AF XY:

0.0275

AC XY:

2047

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.00817

Gnomad4 AMR

AF:

0.0289

Gnomad4 ASJ

AF:

0.0225

Gnomad4 EAS

AF:

0.0699

Gnomad4 SAS

AF:

0.0331

Gnomad4 FIN

AF:

0.00547

Gnomad4 NFE

AF:

0.0427

Gnomad4 OTH

AF:

0.0332

Alfa

AF:

0.0353

Hom.:

Bravo

AF:

0.0303

Asia WGS

AF:

0.0410

AC:

142

AN:

3478

EpiCase

AF:

0.0482

EpiControl

AF:

0.0455

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

1.9

DANN

Benign

0.44

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over