9-100578376-C-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001018116.2(CAVIN4):c.233C>T(p.Ser78Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00125 in 1,613,944 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0065 ( 7 hom., cov: 32)

Exomes 𝑓: 0.00070 ( 10 hom. )

Consequence

CAVIN4
NM_001018116.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.93

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010524869).

BP6

Variant 9-100578376-C-T is Benign according to our data. Variant chr9-100578376-C-T is described in ClinVar as [Benign]. Clinvar id is 226739.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-100578376-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00646 (983/152136) while in subpopulation AFR AF= 0.0228 (945/41494). AF 95% confidence interval is 0.0216. There are 7 homozygotes in gnomad4. There are 471 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAVIN4	NM_001018116.2 link	c.233C>T	p.Ser78Leu	missense_variant	Exon 1 of 2	ENST00000307584.6	NP_001018126.1	Q5BKX8
CAVIN4	XM_047423346.1 link	c.209C>T	p.Ser70Leu	missense_variant	Exon 2 of 3		XP_047279302.1
CAVIN4	XM_047423347.1 link	c.21+1421C>T		intron_variant	Intron 1 of 1		XP_047279303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAVIN4	ENST00000307584.6 link	c.233C>T	p.Ser78Leu	missense_variant	Exon 1 of 2	1	NM_001018116.2	ENSP00000418668.1		Q5BKX8

Frequencies

GnomAD3 genomes

AF:

0.00645

AC:

981

AN:

152018

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0228

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00138

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:

0.0000147

Gnomad OTH

AF:

0.00765

GnomAD3 exomes

AF:

0.00163

AC:

410

AN:

251236

Hom.:

AF XY:

0.00117

AC XY:

159

AN XY:

135752

show subpopulations

Gnomad AFR exome

AF:

0.0236

Gnomad AMR exome

AF:

0.000607

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000703

AC:

1027

AN:

1461808

Hom.:

Cov.:

AF XY:

0.000579

AC XY:

421

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.0254

Gnomad4 AMR exome

AF:

0.000716

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000522

Gnomad4 OTH exome

AF:

0.00124

GnomAD4 genome

AF:

0.00646

AC:

983

AN:

152136

Hom.:

Cov.:

AF XY:

0.00633

AC XY:

471

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0228

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00757

Alfa

AF:

0.00130

Hom.:

Bravo

AF:

0.00736

ESP6500AA

AF:

0.0227

AC:

100

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00214

AC:

260

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:3

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	Ser78Leu in exon 1 of MURC: This variant is not expected to have clinical signif icance because it has been identified in 2.3% (100/4406) of African American chr omosomes from a broad population by the NHLBI Exome Sequencing Project (http://e vs.gs.washington.edu/EVS; dbSNP rs73657328). -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 20, 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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.90

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.90

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.12

Sift

Uncertain

0.018

Sift4G

Benign

0.13

Polyphen

0.89

Vest4

0.34

MVP

0.49

MPC

0.052

ClinPred

0.026

GERP RS

4.1

Varity_R

0.20

gMVP

0.15

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