rs6139004

Positions:

• chr20-3071920-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000915.4(OXT):​c.120+145A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 1,342,624 control chromosomes in the GnomAD database, including 25,827 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 0.18 (2621 hom., cov: 33)
  • Exomes 𝑓: 0.19 (23206 hom.)
• Consequence: OXT NM_000915.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.763

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]

LOC101929098 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OXT	NM_000915.4	c.120+145A>G		intron_variant		ENST00000217386.2	NP_000906.1
LOC101929098	XR_430278.4	n.103+277T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OXT	ENST00000217386.2	c.120+145A>G		intron_variant		1	NM_000915.4	ENSP00000217386.2

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27662 AN: 151616 Hom.: 2614 Cov.: 33

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.0792

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.184

GnomAD4 exome AF: 0.194 AC: 231516 AN: 1190888 Hom.: 23206 Cov.: 20 AF XY: 0.195 AC XY: 113541 AN XY: 581470

Gnomad4 AFR exome AF: 0.168

Gnomad4 AMR exome AF: 0.112

Gnomad4 ASJ exome AF: 0.228

Gnomad4 EAS exome AF: 0.0727

Gnomad4 SAS exome AF: 0.219

Gnomad4 FIN exome AF: 0.224

Gnomad4 NFE exome AF: 0.198

Gnomad4 OTH exome AF: 0.190

GnomAD4 genome AF: 0.182 AC: 27682 AN: 151736 Hom.: 2621 Cov.: 33 AF XY: 0.183 AC XY: 13551 AN XY: 74156

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.0790

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.183

Alfa AF: 0.192 Hom.: 359

Bravo AF: 0.171

Asia WGS AF: 0.133 AC: 464 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.3
DANN	Benign	0.20

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: rs6139004; hg19: chr20-3052566; COSMIC: COSV54131727;