rs237875

Positions:

• chr3-8740720-A-G
• chr3-8740720-A-T

Variant summary

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

The NM_033337.3(CAV3):​c.115-4806A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 151,988 control chromosomes in the GnomAD database, including 20,062 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 0.51 (20062 hom., cov: 32)
• Consequence: CAV3 NM_033337.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAV3	NM_033337.3	c.115-4806A>G		intron_variant		ENST00000343849.3
CAV3	NM_001234.5	c.115-4806A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAV3	ENST00000343849.3	c.115-4806A>G		intron_variant		1	NM_033337.3	P1

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78176 AN: 151868 Hom.: 20030 Cov.: 32

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.515 AC: 78257 AN: 151988 Hom.: 20062 Cov.: 32 AF XY: 0.513 AC XY: 38066 AN XY: 74260

Gnomad4 AFR AF: 0.529

Gnomad4 AMR AF: 0.539

Gnomad4 ASJ AF: 0.421

Gnomad4 EAS AF: 0.394

Gnomad4 SAS AF: 0.472

Gnomad4 FIN AF: 0.489

Gnomad4 NFE AF: 0.523

Gnomad4 OTH AF: 0.514

Alfa AF: 0.507 Hom.: 24678

Bravo AF: 0.514

Asia WGS AF: 0.442 AC: 1535 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.2
DANN	Benign	0.60

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: rs237875; hg19: chr3-8782406;