rs28623148

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001018116.2(CAVIN4):c.570A>T(p.Ser190=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.039 in 1,614,118 control chromosomes in the GnomAD database, including 3,269 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.043 ( 305 hom., cov: 32)

Exomes 𝑓: 0.039 ( 2964 hom. )

Consequence

CAVIN4
NM_001018116.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.468

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 made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 9-100585926-A-T is Benign according to our data. Variant chr9-100585926-A-T is described in ClinVar as [Benign]. Clinvar id is 226741.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.468 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CAVIN4	NM_001018116.2 linkuse as main transcript	c.570A>T	p.Ser190=	synonymous_variant	2/2	ENST00000307584.6
CAVIN4	XM_047423346.1 linkuse as main transcript	c.546A>T	p.Ser182=	synonymous_variant	3/3
CAVIN4	XM_047423347.1 linkuse as main transcript	c.183A>T	p.Ser61=	synonymous_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAVIN4	ENST00000307584.6 linkuse as main transcript	c.570A>T	p.Ser190=	synonymous_variant	2/2	1	NM_001018116.2	P1

Frequencies

GnomAD3 genomes

AF:

0.0434

AC:

6610

AN:

152134

Hom.:

307

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0548

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0327

Gnomad ASJ

AF:

0.0233

Gnomad EAS

AF:

0.204

Gnomad SAS

AF:

0.204

Gnomad FIN

AF:

0.00989

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0221

Gnomad OTH

AF:

0.0426

GnomAD3 exomes

AF:

0.0605

AC:

15184

AN:

251174

Hom.:

1106

AF XY:

0.0655

AC XY:

8894

AN XY:

135738

show subpopulations

Gnomad AFR exome

AF:

0.0543

Gnomad AMR exome

AF:

0.0338

Gnomad ASJ exome

AF:

0.0220

Gnomad EAS exome

AF:

0.215

Gnomad SAS exome

AF:

0.189

Gnomad FIN exome

AF:

0.0109

Gnomad NFE exome

AF:

0.0237

Gnomad OTH exome

AF:

0.0395

GnomAD4 exome

AF:

0.0385

AC:

56339

AN:

1461866

Hom.:

2964

Cov.:

AF XY:

0.0425

AC XY:

30911

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0522

Gnomad4 AMR exome

AF:

0.0352

Gnomad4 ASJ exome

AF:

0.0212

Gnomad4 EAS exome

AF:

0.197

Gnomad4 SAS exome

AF:

0.183

Gnomad4 FIN exome

AF:

0.0121

Gnomad4 NFE exome

AF:

0.0227

Gnomad4 OTH exome

AF:

0.0459

GnomAD4 genome

AF:

0.0434

AC:

6601

AN:

152252

Hom.:

305

Cov.:

AF XY:

0.0460

AC XY:

3423

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0547

Gnomad4 AMR

AF:

0.0326

Gnomad4 ASJ

AF:

0.0233

Gnomad4 EAS

AF:

0.203

Gnomad4 SAS

AF:

0.204

Gnomad4 FIN

AF:

0.00989

Gnomad4 NFE

AF:

0.0221

Gnomad4 OTH

AF:

0.0427

Alfa

AF:

0.0256

Hom.:

Bravo

AF:

0.0428

Asia WGS

AF:

0.212

AC:

737

AN:

3478

EpiCase

AF:

0.0230

EpiControl

AF:

0.0213

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 24, 2014	Ser190Ser in exon 2 of MURC: This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue and is not located withi n the splice consensus sequence. It has been identified in 5.3% (235/4406) of Af rican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs28623148). -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 23, 2016	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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

Cadd

Benign

7.8

Dann

Benign

0.76

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over