rs6115781

Variant names:

• chr20-3072727-G-T
• rs6115781
• NM_000915.4:c.*309G>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000915.4(OXT):​c.*309G>T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0125 in 152,308 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.013 (42 hom., cov: 33)
• Consequence: OXT NM_000915.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.396

Genes affected

OXT (HGNC:8528): (oxytocin/neurophysin I prepropeptide) This gene encodes a precursor protein that is processed to produce oxytocin and neurophysin I. Oxytocin is a posterior pituitary hormone which is synthesized as an inactive precursor in the hypothalamus along with its carrier protein neurophysin I. Together with neurophysin, it is packaged into neurosecretory vesicles and transported axonally to the nerve endings in the neurohypophysis, where it is either stored or secreted into the bloodstream. The precursor seems to be activated while it is being transported along the axon to the posterior pituitary. This hormone contracts smooth muscle during parturition and lactation. It is also involved in cognition, tolerance, adaptation and complex sexual and maternal behaviour, as well as in the regulation of water excretion and cardiovascular functions. [provided by RefSeq, Dec 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0125 (1905/152308) while in subpopulation AFR AF= 0.0428 (1781/41568). AF 95% confidence interval is 0.0412. There are 42 homozygotes in gnomad4. There are 907 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 42 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OXT	NM_000915.4	c.*309G>T		downstream_gene_variant		ENST00000217386.2	NP_000906.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OXT	ENST00000217386.2	c.*309G>T		downstream_gene_variant		1	NM_000915.4	ENSP00000217386.2

Frequencies

GnomAD3 genomes AF: 0.0125 AC: 1897 AN: 152190 Hom.: 42 Cov.: 33

Gnomad AFR AF: 0.0428

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00484

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.00860

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

GnomAD4 genome AF: 0.0125 AC: 1905 AN: 152308 Hom.: 42 Cov.: 33 AF XY: 0.0122 AC XY: 907 AN XY: 74482

Gnomad4 AFR AF: 0.0428

Gnomad4 AMR AF: 0.00483

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.00851

Alfa AF: 0.0168 Hom.: 4

Bravo AF: 0.0147

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.17
DANN	Benign	0.62

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6115781; hg19: chr20-3053373;