rs17297803

Variant names:

• chr3-8741521-A-G
• rs17297803
• NM_033337.3:c.115-4005A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033337.3(CAV3):​c.115-4005A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0929 in 152,134 control chromosomes in the GnomAD database, including 874 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 0.093 (874 hom., cov: 32)
• Consequence: CAV3 NM_033337.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.557
• Publications: 3 publications found

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]

SSUH2 (HGNC:24809): (ssu-2 homolog) Involved in odontogenesis. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAV3	NM_033337.3	c.115-4005A>G		intron_variant	Intron 1 of 1	ENST00000343849.3	NP_203123.1
OXTR	XR_007095681.1	n.2966T>C		non_coding_transcript_exon_variant	Exon 5 of 5
CAV3	NM_001234.5	c.115-4005A>G		intron_variant	Intron 1 of 2		NP_001225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAV3	ENST00000343849.3	c.115-4005A>G		intron_variant	Intron 1 of 1	1	NM_033337.3	ENSP00000341940.2

Frequencies

GnomAD3 genomes AF: 0.0929 AC: 14129 AN: 152018 Hom.: 873 Cov.: 32

Gnomad AFR AF: 0.0257

Gnomad AMI AF: 0.0264

Gnomad AMR AF: 0.0859

Gnomad ASJ AF: 0.0732

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.0287

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.106

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

GnomAD4 genome AF: 0.0929 AC: 14128 AN: 152134 Hom.: 874 Cov.: 32 AF XY: 0.0902 AC XY: 6705 AN XY: 74366

African (AFR) AF: 0.0256 AC: 1064 AN: 41520

American (AMR) AF: 0.0858 AC: 1312 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0732 AC: 254 AN: 3468

East Asian (EAS) AF: 0.00270 AC: 14 AN: 5176

South Asian (SAS) AF: 0.0291 AC: 140 AN: 4808

European-Finnish (FIN) AF: 0.128 AC: 1354 AN: 10586

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.143 AC: 9727 AN: 67976

Other (OTH) AF: 0.105 AC: 222 AN: 2108

Alfa AF: 0.124 Hom.: 641

Bravo AF: 0.0876

Asia WGS AF: 0.0200 AC: 71 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.096
DANN	Benign	0.49
PhyloP100		-0.56
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: rs17297803; hg19: chr3-8783207;