Variant rs2165668 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000509111.2(ENSG00000272297):c.145+21635A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.937 in 1,117,960 control chromosomes in the GnomAD database, including 492,441 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.90 ( 62036 hom., cov: 33)

Exomes 𝑓: 0.94 ( 430405 hom. )

Consequence

ENSG00000272297
ENST00000509111.2 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.21

Variant links:

Genes affected

ENSG00000272297 (HGNC:):

ENSG00000272297 links:

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 4-186533547-T-C is Benign according to our data. Variant chr4-186533547-T-C is described in ClinVar as [Benign]. Clinvar id is 1263722.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105377596	XR_007058498.1 link	n.143+8652T>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000272297	ENST00000509111.2 link	c.145+21635A>G		intron_variant	Intron 1 of 1	3		ENSP00000422449.2		H0Y8X5
MTNR1A	ENST00000703170 link	c.*142A>G		3_prime_UTR_variant	Exon 2 of 2			ENSP00000515216.1		P48039

Frequencies

GnomAD3 genomes

AF:

0.900

AC:

136839

AN:

152090

Hom.:

62007

Cov.:

show subpopulations

Gnomad AFR

AF:

0.773

Gnomad AMI

AF:

0.965

Gnomad AMR

AF:

0.944

Gnomad ASJ

AF:

0.887

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.925

Gnomad FIN

AF:

0.954

Gnomad MID

AF:

0.943

Gnomad NFE

AF:

0.948

Gnomad OTH

AF:

0.912

GnomAD4 exome

AF:

0.943

AC:

911103

AN:

965752

Hom.:

430405

AF XY:

0.942

AC XY:

466066

AN XY:

494604

show subpopulations

Gnomad4 AFR exome

AF:

0.773

Gnomad4 AMR exome

AF:

0.961

Gnomad4 ASJ exome

AF:

0.880

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.919

Gnomad4 FIN exome

AF:

0.955

Gnomad4 NFE exome

AF:

0.950

Gnomad4 OTH exome

AF:

0.934

GnomAD4 genome

AF:

0.900

AC:

136920

AN:

152208

Hom.:

62036

Cov.:

AF XY:

0.901

AC XY:

67042

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.773

Gnomad4 AMR

AF:

0.945

Gnomad4 ASJ

AF:

0.887

Gnomad4 EAS

AF:

0.999

Gnomad4 SAS

AF:

0.924

Gnomad4 FIN

AF:

0.954

Gnomad4 NFE

AF:

0.948

Gnomad4 OTH

AF:

0.913

Alfa

AF:

0.929

Hom.:

15246

Bravo

AF:

0.895

Asia WGS

AF:

0.951

AC:

3308

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 13, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.091

DANN

Benign

0.43

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