rs1051992

Variant names:

• chr11-6319476-A-G
• rs1051992
• NM_145040.3:c.473T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-6319476-A-G
• chr11-6319476-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000303927.4(CAVIN3):​c.473T>C​(p.Leu158Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 1,606,178 control chromosomes in the GnomAD database, including 239,745 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict 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 (20612 hom., cov: 34)
  • Exomes 𝑓: 0.55 (219133 hom.)
• Consequence: CAVIN3 ENST00000303927.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72
• Publications: 45 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.296233E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000303927.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAVIN3	NM_145040.3	MANE Select	c.473T>C	p.Leu158Pro	missense	Exon 2 of 2	NP_659477.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAVIN3	ENST00000303927.4	TSL:1 MANE Select	c.473T>C	p.Leu158Pro	missense	Exon 2 of 2	ENSP00000307292.3
	CAVIN3	ENST00000530979.1	TSL:2	c.569T>C	p.Leu190Pro	missense	Exon 3 of 3	ENSP00000432047.1
	CAVIN3	ENST00000524852.1	TSL:3	n.259T>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78272 AN: 152032 Hom.: 20604 Cov.: 34

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.601

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.498

GnomAD2 exomes AF: 0.550 AC: 130009 AN: 236392 AF XY: 0.559

Gnomad AFR exome AF: 0.389

Gnomad AMR exome AF: 0.455

Gnomad ASJ exome AF: 0.527

Gnomad EAS exome AF: 0.648

Gnomad FIN exome AF: 0.639

Gnomad NFE exome AF: 0.555

Gnomad OTH exome AF: 0.547

GnomAD4 exome AF: 0.547 AC: 795125 AN: 1454026 Hom.: 219133 Cov.: 62 AF XY: 0.550 AC XY: 397635 AN XY: 723450

African (AFR) AF: 0.388 AC: 12948 AN: 33366

American (AMR) AF: 0.463 AC: 20453 AN: 44156

Ashkenazi Jewish (ASJ) AF: 0.535 AC: 13834 AN: 25872

East Asian (EAS) AF: 0.612 AC: 24302 AN: 39678

South Asian (SAS) AF: 0.612 AC: 52406 AN: 85672

European-Finnish (FIN) AF: 0.640 AC: 31338 AN: 48960

Middle Eastern (MID) AF: 0.496 AC: 2851 AN: 5752

European-Non Finnish (NFE) AF: 0.545 AC: 604728 AN: 1110446

Other (OTH) AF: 0.537 AC: 32265 AN: 60124

GnomAD4 genome AF: 0.515 AC: 78313 AN: 152152 Hom.: 20612 Cov.: 34 AF XY: 0.520 AC XY: 38703 AN XY: 74394

African (AFR) AF: 0.395 AC: 16411 AN: 41520

American (AMR) AF: 0.507 AC: 7749 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 1880 AN: 3466

East Asian (EAS) AF: 0.633 AC: 3274 AN: 5174

South Asian (SAS) AF: 0.602 AC: 2906 AN: 4828

European-Finnish (FIN) AF: 0.644 AC: 6818 AN: 10582

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.551 AC: 37444 AN: 67976

Other (OTH) AF: 0.495 AC: 1047 AN: 2114

Alfa AF: 0.542 Hom.: 69871

Bravo AF: 0.494

TwinsUK AF: 0.536 AC: 1988

ALSPAC AF: 0.545 AC: 2101

ESP6500AA AF: 0.396 AC: 1736

ESP6500EA AF: 0.540 AC: 4636

ExAC AF: 0.549 AC: 66493

Asia WGS AF: 0.579 AC: 2018 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.036
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	3.6
DANN	Benign	0.62
DEOGEN2	Benign	0.027	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0038	N
LIST_S2	Benign	0.41	T
MetaRNN	Benign	0.0000033	T
MetaSVM	Benign	-0.93	T
PhyloP100		-1.7
PrimateAI	Benign	0.38	T
PROVEAN	Benign	0.19	N
REVEL	Benign	0.023
Sift	Benign	0.26	T
Sift4G	Benign	0.31	T
Polyphen		0.0	B
Vest4		0.093
MPC		0.57
ClinPred		0.0056	T
GERP RS		-3.6
Varity_R		0.10
gMVP		0.039
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1051992; hg19: chr11-6340706; COSMIC: COSV58268956; COSMIC: COSV58268956;