4-186534710-AG-A

Position:

• chr4-186534710-AG-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005958.4(MTNR1A):​c.185-154del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.93 (65963 hom., cov: 0)
• Consequence: MTNR1A NM_005958.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00

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]

LOC105377596 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 4-186534710-AG-A is Benign according to our data. Variant chr4-186534710-AG-A is described in ClinVar as [Benign]. Clinvar id is 1181324.Status of the report is criteria_provided_single_submitter, 1 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
MTNR1A	NM_005958.4	c.185-154del		intron_variant		ENST00000307161.5	NP_005949.1
LOC105377596	XR_007058498.1	n.143+9818del		intron_variant, non_coding_transcript_variant
MTNR1A	XM_011532002.4	c.-71-154del		intron_variant			XP_011530304.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTNR1A	ENST00000307161.5	c.185-154del		intron_variant		1	NM_005958.4	ENSP00000302811	P1
MTNR1A	ENST00000703170.1	c.185-154del		intron_variant				ENSP00000515216	P1

Frequencies

GnomAD3 genomes AF: 0.931 AC: 141502 AN: 152034 Hom.: 65928 Cov.: 0

Gnomad AFR AF: 0.884

Gnomad AMI AF: 0.965

Gnomad AMR AF: 0.950

Gnomad ASJ AF: 0.887

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.924

Gnomad FIN AF: 0.955

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.948

Gnomad OTH AF: 0.927

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

GnomAD4 genome AF: 0.931 AC: 141590 AN: 152152 Hom.: 65963 Cov.: 0 AF XY: 0.931 AC XY: 69282 AN XY: 74404

Gnomad4 AFR AF: 0.883

Gnomad4 AMR AF: 0.950

Gnomad4 ASJ AF: 0.887

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.923

Gnomad4 FIN AF: 0.955

Gnomad4 NFE AF: 0.948

Gnomad4 OTH AF: 0.927

Alfa AF: 0.939 Hom.: 8170

Bravo AF: 0.929

Asia WGS AF: 0.962 AC: 3346 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

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: rs60023119; hg19: chr4-187455864;