rs237872

Positions:

• chr3-8738752-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+4762C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 152,086 control chromosomes in the GnomAD database, including 23,412 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 0.55 (23412 hom., cov: 32)
• Consequence: CAV3 NM_033337.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.35

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:):

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAV3	NM_033337.3	c.114+4762C>T		intron_variant		ENST00000343849.3	NP_203123.1
CAV3	NM_001234.5	c.114+4762C>T		intron_variant			NP_001225.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAV3	ENST00000343849.3	c.114+4762C>T		intron_variant		1	NM_033337.3	ENSP00000341940.2

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82819 AN: 151966 Hom.: 23356 Cov.: 32

Gnomad AFR AF: 0.709

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.451

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.514

Gnomad OTH AF: 0.529

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

GnomAD4 genome AF: 0.545 AC: 82924 AN: 152086 Hom.: 23412 Cov.: 32 AF XY: 0.537 AC XY: 39940 AN XY: 74344

Gnomad4 AFR AF: 0.710

Gnomad4 AMR AF: 0.455

Gnomad4 ASJ AF: 0.418

Gnomad4 EAS AF: 0.297

Gnomad4 SAS AF: 0.451

Gnomad4 FIN AF: 0.451

Gnomad4 NFE AF: 0.514

Gnomad4 OTH AF: 0.526

Alfa AF: 0.560 Hom.: 3554

Bravo AF: 0.548

Asia WGS AF: 0.395 AC: 1373 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0020
DANN	Benign	0.59

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: rs237872; hg19: chr3-8780438;