4-186533547-T-C

Position:

• chr4-186533547-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The XR_007058498.1(LOC105377596):​n.143+8652T>C variant causes a intron, non coding transcript 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: LOC105377596 XR_007058498.1 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.21

Genes affected

LOC105377596 (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

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/exons	MANE	Protein	UniProt
LOC105377596	XR_007058498.1	n.143+8652T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTNR1A	ENST00000703170.1	c.*142A>G		3_prime_UTR_variant	2/2			ENSP00000515216	P1

Frequencies

GnomAD3 genomes AF: 0.900 AC: 136839 AN: 152090 Hom.: 62007 Cov.: 33

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

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.: 33 AF XY: 0.901 AC XY: 67042 AN XY: 74422

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

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 13, 2021	- -

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

Other links and lift over

dbSNP: rs2165668; hg19: chr4-187454701;