Genetic Variant CAVIN4:c.408+181G>A (chr9-100578732-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001018116.2(CAVIN4):c.408+181G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 151,932 control chromosomes in the GnomAD database, including 24,154 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.56 ( 24154 hom., cov: 32)

Consequence

CAVIN4
NM_001018116.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.79

Publications

3 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 9-100578732-G-A is Benign according to our data. Variant chr9-100578732-G-A is described in ClinVar as Benign. ClinVar VariationId is 674703.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.616 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAVIN4	NM_001018116.2	MANE Select	c.408+181G>A		intron	N/A	NP_001018126.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAVIN4	ENST00000307584.6	TSL:1 MANE Select	c.408+181G>A		intron	N/A	ENSP00000418668.1

Frequencies

GnomAD3 genomes

AF:

0.557

AC:

84543

AN:

151814

Hom.:

24130

Cov.:

show subpopulations

Gnomad AFR

AF:

0.462

Gnomad AMI

AF:

0.685

Gnomad AMR

AF:

0.626

Gnomad ASJ

AF:

0.620

Gnomad EAS

AF:

0.295

Gnomad SAS

AF:

0.626

Gnomad FIN

AF:

0.500

Gnomad MID

AF:

0.620

Gnomad NFE

AF:

0.617

Gnomad OTH

AF:

0.587

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.557

AC:

84623

AN:

151932

Hom.:

24154

Cov.:

AF XY:

0.554

AC XY:

41140

AN XY:

74222

show subpopulations

African (AFR)

AF:

0.463

AC:

19157

AN:

41418

American (AMR)

AF:

0.626

AC:

9558

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.620

AC:

2153

AN:

3470

East Asian (EAS)

AF:

0.294

AC:

1516

AN:

5162

South Asian (SAS)

AF:

0.627

AC:

3019

AN:

4814

European-Finnish (FIN)

AF:

0.500

AC:

5265

AN:

10528

Middle Eastern (MID)

AF:

0.619

AC:

182

AN:

294

European-Non Finnish (NFE)

AF:

0.617

AC:

41920

AN:

67958

Other (OTH)

AF:

0.582

AC:

1228

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1888

3777

5665

7554

9442

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

728

1456

2184

2912

3640

<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:

0.598

Hom.:

122559

Bravo

AF:

0.558

Asia WGS

AF:

0.480

AC:

1670

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 18, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.12

(source)

DANN

Benign

0.47

PhyloP100

-4.8

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over