rs6139004

Variant names:

• chr20-3071920-A-G
• rs6139004
• NM_000915.4:c.120+145A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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]

ENSG00000305741 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000915.4. 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
	OXT	NM_000915.4	MANE Select	c.120+145A>G		intron	N/A	NP_000906.1	P01178

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OXT	ENST00000217386.2	TSL:1 MANE Select	c.120+145A>G		intron	N/A	ENSP00000217386.2	P01178
	ENSG00000305741	ENST00000812739.1		n.88+277T>C		intron	N/A
	ENSG00000305741	ENST00000812740.1		n.-66T>C		upstream_gene	N/A

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

African (AFR) AF: 0.168 AC: 3935 AN: 23426

American (AMR) AF: 0.112 AC: 1871 AN: 16776

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 3975 AN: 17400

East Asian (EAS) AF: 0.0727 AC: 2251 AN: 30946

South Asian (SAS) AF: 0.219 AC: 12760 AN: 58280

European-Finnish (FIN) AF: 0.224 AC: 6684 AN: 29818

Middle Eastern (MID) AF: 0.194 AC: 663 AN: 3426

European-Non Finnish (NFE) AF: 0.198 AC: 189870 AN: 960712

Other (OTH) AF: 0.190 AC: 9507 AN: 50104

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

African (AFR) AF: 0.165 AC: 6818 AN: 41356

American (AMR) AF: 0.131 AC: 1998 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 835 AN: 3470

East Asian (EAS) AF: 0.0790 AC: 404 AN: 5114

South Asian (SAS) AF: 0.208 AC: 1000 AN: 4812

European-Finnish (FIN) AF: 0.233 AC: 2456 AN: 10548

Middle Eastern (MID) AF: 0.234 AC: 68 AN: 290

European-Non Finnish (NFE) AF: 0.199 AC: 13519 AN: 67868

Other (OTH) AF: 0.183 AC: 384 AN: 2100

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.3
DANN	Benign	0.20
PhyloP100		-0.76
PromoterAI		0.035	Neutral
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: rs6139004; hg19: chr20-3052566; COSMIC: COSV54131727;