rs1226588

Variant names:

• chr9-100578732-G-A
• rs1226588
• NM_001018116.2:c.408+181G>A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.79

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAVIN4	NM_001018116.2	c.408+181G>A		intron_variant	Intron 1 of 1	ENST00000307584.6	NP_001018126.1
CAVIN4	XM_047423346.1	c.384+181G>A		intron_variant	Intron 2 of 2		XP_047279302.1
CAVIN4	XM_047423347.1	c.21+1777G>A		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	c.408+181G>A		intron_variant	Intron 1 of 1	1	NM_001018116.2	ENSP00000418668.1

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84543 AN: 151814 Hom.: 24130 Cov.: 32

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.: 32 AF XY: 0.554 AC XY: 41140 AN XY: 74222

Gnomad4 AFR AF: 0.463

Gnomad4 AMR AF: 0.626

Gnomad4 ASJ AF: 0.620

Gnomad4 EAS AF: 0.294

Gnomad4 SAS AF: 0.627

Gnomad4 FIN AF: 0.500

Gnomad4 NFE AF: 0.617

Gnomad4 OTH AF: 0.582

Alfa AF: 0.606 Hom.: 62317

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

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.12
DANN	Benign	0.47

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

Other links and lift over

dbSNP: rs1226588; hg19: chr9-103341014;