rs111884608

Variant names:

• chr9-100585844-A-G
• rs111884608
• NM_001018116.2:c.488A>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001018116.2(CAVIN4):​c.488A>G​(p.Asp163Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000769 in 1,614,168 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0041 (6 hom., cov: 32)
  • Exomes 𝑓: 0.00042 (5 hom.)
• Consequence: CAVIN4 NM_001018116.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 3.68
• Publications: 1 publications found

Genes affected

CAVIN4 (HGNC:33742): (caveolae associated protein 4) This gene encodes a protein containing two coiled-coil regions. The encoded protein promotes Rho/ROCK (Rho-kinase) signaling in cardiac muscles cells, and may facilitate myofibrillar organization. [provided by RefSeq, Jun 2013]

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0030948818).
• BP6: Variant 9-100585844-A-G is Benign according to our data. Variant chr9-100585844-A-G is described in ClinVar as Benign. ClinVar VariationId is 226740.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001018116.2. 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
	CAVIN4	NM_001018116.2	MANE Select	c.488A>G	p.Asp163Gly	missense	Exon 2 of 2	NP_001018126.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAVIN4	ENST00000307584.6	TSL:1 MANE Select	c.488A>G	p.Asp163Gly	missense	Exon 2 of 2	ENSP00000418668.1

Frequencies

GnomAD3 genomes AF: 0.00413 AC: 628 AN: 152194 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0143

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.00113 AC: 285 AN: 251230 AF XY: 0.000862

Gnomad AFR exome AF: 0.0151

Gnomad AMR exome AF: 0.000896

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000417 AC: 609 AN: 1461856 Hom.: 5 Cov.: 32 AF XY: 0.000399 AC XY: 290 AN XY: 727228

African (AFR) AF: 0.0142 AC: 476 AN: 33478

American (AMR) AF: 0.00103 AC: 46 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5768

European-Non Finnish (NFE) AF: 0.0000216 AC: 24 AN: 1111976

Other (OTH) AF: 0.000828 AC: 50 AN: 60396

GnomAD4 genome AF: 0.00415 AC: 632 AN: 152312 Hom.: 6 Cov.: 32 AF XY: 0.00397 AC XY: 296 AN XY: 74486

African (AFR) AF: 0.0143 AC: 596 AN: 41572

American (AMR) AF: 0.00183 AC: 28 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68020

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00166 Hom.: 4

Bravo AF: 0.00476

ESP6500AA AF: 0.0166 AC: 73

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00152 AC: 184

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	13
DANN	Benign	0.97
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.47
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.57	T
MetaRNN	Benign	0.0031	T
MetaSVM	Benign	-1.0	T
PhyloP100		3.7
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.13
Sift	Benign	0.21	T
Sift4G	Benign	0.064	T
Polyphen		0.16	B
Vest4		0.081
MVP		0.11
MPC		0.056
ClinPred		0.014	T
GERP RS		2.9
Varity_R		0.078
gMVP		0.11
Mutation Taster		=93/7	polymorphism

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: rs111884608; hg19: chr9-103348126;