rs4686300

Positions:

• chr3-8737062-C-T

Variant summary

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

The NM_033337.3(CAV3):​c.114+3072C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0497 in 152,100 control chromosomes in the GnomAD database, including 339 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 0.050 (339 hom., cov: 32)
• Consequence: CAV3 NM_033337.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.510

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAV3	NM_033337.3	c.114+3072C>T		intron_variant		ENST00000343849.3	NP_203123.1
CAV3	NM_001234.5	c.114+3072C>T		intron_variant			NP_001225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAV3	ENST00000343849.3	c.114+3072C>T		intron_variant		1	NM_033337.3	ENSP00000341940	P1

Frequencies

GnomAD3 genomes AF: 0.0497 AC: 7550 AN: 151982 Hom.: 339 Cov.: 32

Gnomad AFR AF: 0.0347

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0557

Gnomad ASJ AF: 0.0355

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.0866

Gnomad FIN AF: 0.0998

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0356

Gnomad OTH AF: 0.0344

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

GnomAD4 genome AF: 0.0497 AC: 7557 AN: 152100 Hom.: 339 Cov.: 32 AF XY: 0.0542 AC XY: 4030 AN XY: 74354

Gnomad4 AFR AF: 0.0346

Gnomad4 AMR AF: 0.0562

Gnomad4 ASJ AF: 0.0355

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.0869

Gnomad4 FIN AF: 0.0998

Gnomad4 NFE AF: 0.0356

Gnomad4 OTH AF: 0.0340

Alfa AF: 0.0436 Hom.: 29

Bravo AF: 0.0476

Asia WGS AF: 0.147 AC: 512 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	10
DANN	Benign	0.37

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: rs4686300; hg19: chr3-8778748;