rs751703046

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001018116.2(CAVIN4):​c.920G>A​(p.Ser307Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,445,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CAVIN4
NM_001018116.2 missense

Scores

18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.24
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.034679472).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CAVIN4NM_001018116.2 linkc.920G>A p.Ser307Asn missense_variant Exon 2 of 2 ENST00000307584.6 NP_001018126.1 Q5BKX8
CAVIN4XM_047423346.1 linkc.896G>A p.Ser299Asn missense_variant Exon 3 of 3 XP_047279302.1
CAVIN4XM_047423347.1 linkc.533G>A p.Ser178Asn missense_variant Exon 2 of 2 XP_047279303.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CAVIN4ENST00000307584.6 linkc.920G>A p.Ser307Asn missense_variant Exon 2 of 2 1 NM_001018116.2 ENSP00000418668.1 Q5BKX8

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.92e-7
AC:
1
AN:
1445380
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
716860
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.079
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.64
CADD
Benign
5.8
DANN
Benign
0.90
DEOGEN2
Benign
0.018
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.079
N
LIST_S2
Benign
0.42
T
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.035
T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-0.47
N
REVEL
Benign
0.040
Sift
Benign
0.30
T
Sift4G
Benign
0.28
T
Polyphen
0.0010
B
Vest4
0.035
MutPred
0.14
Loss of phosphorylation at S307 (P = 0.0091);
MVP
0.088
MPC
0.036
ClinPred
0.034
T
GERP RS
0.27
Varity_R
0.039
gMVP
0.044

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-103348558; API