11-6319295-A-T

Position:

• chr11-6319295-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_145040.3(CAVIN3):​c.654T>A​(p.Ala218Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 1,608,630 control chromosomes in the GnomAD database, including 375,733 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 0.65 (33020 hom., cov: 34)
  • Exomes 𝑓: 0.68 (342713 hom.)
• Consequence: CAVIN3 NM_145040.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.254

Genes affected

CAVIN3 (HGNC:9400): (caveolae associated protein 3) The protein encoded by this gene was identified as a binding protein of the protein kinase C, delta (PRKCD). The expression of this gene in cultured cell lines is strongly induced by serum starvation. The expression of this protein was found to be down-regulated in various cancer cell lines, suggesting the possible tumor suppressor function of this protein. [provided by RefSeq, Jul 2008]

CAVIN3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP7: Synonymous conserved (PhyloP=-0.254 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAVIN3	NM_145040.3	c.654T>A	p.Ala218Ala	synonymous_variant	2/2	ENST00000303927.4	NP_659477.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAVIN3	ENST00000303927.4	c.654T>A	p.Ala218Ala	synonymous_variant	2/2	1	NM_145040.3	ENSP00000307292.3

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99526 AN: 151998 Hom.: 33010 Cov.: 34

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.827

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.707

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.708

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.650

GnomAD3 exomes AF: 0.682 AC: 165955 AN: 243258 Hom.: 57224 AF XY: 0.690 AC XY: 91235 AN XY: 132170

Gnomad AFR exome AF: 0.547

Gnomad AMR exome AF: 0.562

Gnomad ASJ exome AF: 0.713

Gnomad EAS exome AF: 0.764

Gnomad SAS exome AF: 0.715

Gnomad FIN exome AF: 0.753

Gnomad NFE exome AF: 0.699

Gnomad OTH exome AF: 0.693

GnomAD4 exome AF: 0.685 AC: 997331 AN: 1456514 Hom.: 342713 Cov.: 74 AF XY: 0.687 AC XY: 497241 AN XY: 724268

Gnomad4 AFR exome AF: 0.547

Gnomad4 AMR exome AF: 0.572

Gnomad4 ASJ exome AF: 0.715

Gnomad4 EAS exome AF: 0.718

Gnomad4 SAS exome AF: 0.714

Gnomad4 FIN exome AF: 0.751

Gnomad4 NFE exome AF: 0.686

Gnomad4 OTH exome AF: 0.678

GnomAD4 genome AF: 0.655 AC: 99575 AN: 152116 Hom.: 33020 Cov.: 34 AF XY: 0.657 AC XY: 48877 AN XY: 74348

Gnomad4 AFR AF: 0.553

Gnomad4 AMR AF: 0.623

Gnomad4 ASJ AF: 0.707

Gnomad4 EAS AF: 0.745

Gnomad4 SAS AF: 0.710

Gnomad4 FIN AF: 0.747

Gnomad4 NFE AF: 0.694

Gnomad4 OTH AF: 0.647

Alfa AF: 0.673 Hom.: 8440

Bravo AF: 0.638

Asia WGS AF: 0.688 AC: 2396 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.9
DANN	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12570; hg19: chr11-6340525; COSMIC: COSV58268941; COSMIC: COSV58268941;