dbSNP rs2780956: CAVIN4:p.Arg332Arg (chr9-100586352-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001018116.2(CAVIN4):c.996G>A(p.Arg332Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 1,613,218 control chromosomes in the GnomAD database, including 129,738 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 10826 hom., cov: 30)

Exomes 𝑓: 0.40 ( 118912 hom. )

Consequence

CAVIN4
NM_001018116.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.338

Publications

15 publications found

Variant links:

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]

CAVIN4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 9-100586352-G-A is Benign according to our data. Variant chr9-100586352-G-A is described in ClinVar as Benign. ClinVar VariationId is 226743.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.338 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAVIN4	NM_001018116.2	MANE Select	c.996G>A	p.Arg332Arg	synonymous	Exon 2 of 2	NP_001018126.1	Q5BKX8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAVIN4	ENST00000307584.6	TSL:1 MANE Select	c.996G>A	p.Arg332Arg	synonymous	Exon 2 of 2	ENSP00000418668.1	Q5BKX8
	CAVIN4	ENST00000956994.1		c.993G>A	p.Arg331Arg	synonymous	Exon 2 of 2	ENSP00000627053.1

Frequencies

GnomAD3 genomes

AF:

0.367

AC:

55637

AN:

151482

Hom.:

10815

Cov.:

show subpopulations

Gnomad AFR

AF:

0.282

Gnomad AMI

AF:

0.480

Gnomad AMR

AF:

0.448

Gnomad ASJ

AF:

0.430

Gnomad EAS

AF:

0.0911

Gnomad SAS

AF:

0.315

Gnomad FIN

AF:

0.407

Gnomad MID

AF:

0.325

Gnomad NFE

AF:

0.415

Gnomad OTH

AF:

0.381

GnomAD2 exomes

AF:

0.379

AC:

95185

AN:

251062

AF XY:

0.375

show subpopulations

Gnomad AFR exome

AF:

0.281

Gnomad AMR exome

AF:

0.518

Gnomad ASJ exome

AF:

0.425

Gnomad EAS exome

AF:

0.0872

Gnomad FIN exome

AF:

0.403

Gnomad NFE exome

AF:

0.405

Gnomad OTH exome

AF:

0.381

GnomAD4 exome

AF:

0.397

AC:

580482

AN:

1461614

Hom.:

118912

Cov.:

AF XY:

0.395

AC XY:

287097

AN XY:

727090

show subpopulations

African (AFR)

AF:

0.274

AC:

9161

AN:

33478

American (AMR)

AF:

0.511

AC:

22864

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.426

AC:

11135

AN:

26126

East Asian (EAS)

AF:

0.0738

AC:

2929

AN:

39696

South Asian (SAS)

AF:

0.324

AC:

27967

AN:

86198

European-Finnish (FIN)

AF:

0.402

AC:

21444

AN:

53380

Middle Eastern (MID)

AF:

0.326

AC:

1880

AN:

5764

European-Non Finnish (NFE)

AF:

0.414

AC:

460185

AN:

1111870

Other (OTH)

AF:

0.379

AC:

22917

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

19189

38378

57567

76756

95945

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14008

28016

42024

56032

70040

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.367

AC:

55700

AN:

151604

Hom.:

10826

Cov.:

AF XY:

0.367

AC XY:

27197

AN XY:

74100

show subpopulations

African (AFR)

AF:

0.282

AC:

11646

AN:

41282

American (AMR)

AF:

0.449

AC:

6840

AN:

15248

Ashkenazi Jewish (ASJ)

AF:

0.430

AC:

1491

AN:

3466

East Asian (EAS)

AF:

0.0911

AC:

469

AN:

5148

South Asian (SAS)

AF:

0.316

AC:

1509

AN:

4780

European-Finnish (FIN)

AF:

0.407

AC:

4276

AN:

10502

Middle Eastern (MID)

AF:

0.318

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.415

AC:

28143

AN:

67876

Other (OTH)

AF:

0.379

AC:

795

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1706

3411

5117

6822

8528

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

534

1068

1602

2136

2670

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.401

Hom.:

4071

Bravo

AF:

0.365

Asia WGS

AF:

0.210

AC:

730

AN:

3478

EpiCase

AF:

0.413

EpiControl

AF:

0.406

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (2)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

2.8

(source)

DANN

Benign

0.54

PhyloP100

0.34

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over