rs11720238

Positions:

• chr3-8749653-G-A
• chr3-8749653-G-T

Variant summary

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

The ENST00000472766.1(CAV3):​n.155+15663G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0196 in 152,196 control chromosomes in the GnomAD database, including 45 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 0.020 (45 hom., cov: 33)
• Consequence: CAV3 ENST00000472766.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.142

Genes affected

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]

OXTR (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0196 (2983/152196) while in subpopulation NFE AF= 0.0303 (2062/68004). AF 95% confidence interval is 0.0292. There are 45 homozygotes in gnomad4. There are 1406 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2983 AD,Digenic gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OXTR	XR_007095681.1	n.1884+3231C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAV3	ENST00000472766.1	n.155+15663G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0196 AC: 2985 AN: 152078 Hom.: 45 Cov.: 33

Gnomad AFR AF: 0.00633

Gnomad AMI AF: 0.0473

Gnomad AMR AF: 0.0193

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.00745

Gnomad FIN AF: 0.0124

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.0303

Gnomad OTH AF: 0.0162

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

GnomAD4 genome AF: 0.0196 AC: 2983 AN: 152196 Hom.: 45 Cov.: 33 AF XY: 0.0189 AC XY: 1406 AN XY: 74418

Gnomad4 AFR AF: 0.00629

Gnomad4 AMR AF: 0.0193

Gnomad4 ASJ AF: 0.0334

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.00746

Gnomad4 FIN AF: 0.0124

Gnomad4 NFE AF: 0.0303

Gnomad4 OTH AF: 0.0156

Alfa AF: 0.00234 Hom.: 236

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.3
DANN	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11720238; hg19: chr3-8791339;