rs2254298

chr3-8760542-G-Achr3-8760542-G-T

Variant summary

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

The NM_000916.4(OXTR):c.922+6724C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,206 control chromosomes in the GnomAD database, including 2,317 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 0.16 (2317 hom., cov: 33)
• Consequence: OXTR NM_000916.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.242

Genes affected

OXTR (HGNC:8529): (oxytocin receptor) The protein encoded by this gene belongs to the G-protein coupled receptor family and acts as a receptor for oxytocin. Its activity is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system. The oxytocin-oxytocin receptor system plays an important role in the uterus during parturition. [provided by RefSeq, Jul 2008]

CAV3 (HGNC:1529): (caveolin 3) This gene encodes a caveolin family member, which functions as a component of the caveolae plasma membranes found in most cell types. Caveolin proteins are proposed to be scaffolding proteins for organizing and concentrating certain caveolin-interacting molecules. Mutations identified in this gene lead to interference with protein oligomerization or intra-cellular routing, disrupting caveolae formation and resulting in Limb-Girdle muscular dystrophy type-1C (LGMD-1C), hyperCKemia or rippling muscle disease (RMD). Alternative splicing has been identified for this locus, with inclusion or exclusion of a differentially spliced intron. In addition, transcripts utilize multiple polyA sites and contain two potential translation initiation sites. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OXTR	NM_000916.4	c.922+6724C>T		intron_variant		ENST00000316793.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OXTR	ENST00000316793.8	c.922+6724C>T		intron_variant		1	NM_000916.4	P1
CAV3	ENST00000472766.1	n.156-16935G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24436 AN: 152088 Hom.: 2310 Cov.: 33

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.0735

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.161 AC: 24485 AN: 152206 Hom.: 2317 Cov.: 33 AF XY: 0.161 AC XY: 11963 AN XY: 74420

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.313

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.0735

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.182

Alfa AF: 0.140 Hom.: 559

Bravo AF: 0.177

Asia WGS AF: 0.245 AC: 850 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.1
DANN	Benign	0.35

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: rs2254298; hg19: chr3-8802228;