chr4-186534710-AG-A

Variant names:

• chr4-186534710-AG-A
• rs60023119
• NM_005958.4:c.185-154delC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005958.4(MTNR1A):​c.185-154delC 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
• Publications: 1 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 -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005958.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTNR1A	NM_005958.4	MANE Select	c.185-154delC		intron	N/A	NP_005949.1	P48039

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MTNR1A	ENST00000307161.5	TSL:1 MANE Select	c.185-154delC		intron	N/A	ENSP00000302811.5	P48039
	ENSG00000272297	ENST00000509111.2	TSL:3	c.145+20471delC		intron	N/A	ENSP00000422449.2	H0Y8X5
	MTNR1A	ENST00000703170.1		c.185-154delC		intron	N/A	ENSP00000515216.1	P48039

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

African (AFR) AF: 0.883 AC: 36661 AN: 41498

American (AMR) AF: 0.950 AC: 14533 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.887 AC: 3075 AN: 3468

East Asian (EAS) AF: 0.999 AC: 5155 AN: 5158

South Asian (SAS) AF: 0.923 AC: 4445 AN: 4814

European-Finnish (FIN) AF: 0.955 AC: 10125 AN: 10600

Middle Eastern (MID) AF: 0.952 AC: 280 AN: 294

European-Non Finnish (NFE) AF: 0.948 AC: 64479 AN: 68000

Other (OTH) AF: 0.927 AC: 1957 AN: 2110

Alfa AF: 0.939 Hom.: 8170

Bravo AF: 0.929

Asia WGS AF: 0.962 AC: 3346 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs60023119; hg19: chr4-187455864;