11-6319295-A-T

Variant names:

• chr11-6319295-A-T
• rs12570
• NM_145040.3:c.654T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 publications found

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]

ENSG00000282556 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145040.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAVIN3	NM_145040.3	MANE Select	c.654T>A	p.Ala218Ala	synonymous	Exon 2 of 2	NP_659477.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAVIN3	ENST00000303927.4	TSL:1 MANE Select	c.654T>A	p.Ala218Ala	synonymous	Exon 2 of 2	ENSP00000307292.3	Q969G5
	CAVIN3	ENST00000530979.1	TSL:2	c.750T>A	p.Ala250Ala	synonymous	Exon 3 of 3	ENSP00000432047.1	E9PIE3
	CAVIN3	ENST00000954671.1		c.669T>A	p.Ala223Ala	synonymous	Exon 3 of 3	ENSP00000624730.1

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

GnomAD2 exomes AF: 0.682 AC: 165955 AN: 243258 AF XY: 0.690

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 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

African (AFR) AF: 0.547 AC: 18175 AN: 33216

American (AMR) AF: 0.572 AC: 25042 AN: 43782

Ashkenazi Jewish (ASJ) AF: 0.715 AC: 18464 AN: 25816

East Asian (EAS) AF: 0.718 AC: 28437 AN: 39632

South Asian (SAS) AF: 0.714 AC: 61131 AN: 85564

European-Finnish (FIN) AF: 0.751 AC: 39943 AN: 53182

Middle Eastern (MID) AF: 0.670 AC: 3813 AN: 5688

European-Non Finnish (NFE) AF: 0.686 AC: 761574 AN: 1109562

Other (OTH) AF: 0.678 AC: 40752 AN: 60072

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

African (AFR) AF: 0.553 AC: 22919 AN: 41482

American (AMR) AF: 0.623 AC: 9534 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.707 AC: 2452 AN: 3470

East Asian (EAS) AF: 0.745 AC: 3846 AN: 5164

South Asian (SAS) AF: 0.710 AC: 3429 AN: 4832

European-Finnish (FIN) AF: 0.747 AC: 7901 AN: 10574

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.694 AC: 47156 AN: 67982

Other (OTH) AF: 0.647 AC: 1365 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.9
DANN	Benign	0.84
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12570; hg19: chr11-6340525; COSMIC: COSV58268941; COSMIC: COSV58268941;