9-100578087-G-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.-57G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 1,589,798 control chromosomes in the GnomAD database, including 130,540 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.37 (11237 hom., cov: 32)
  • Exomes 𝑓: 0.40 (119303 hom.)
• Consequence: CAVIN4 NM_001018116.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.58

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=-0.5).
• BP6: Variant 9-100578087-G-A is Benign according to our data. Variant chr9-100578087-G-A is described in ClinVar as [Benign]. Clinvar id is 674700.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAVIN4	NM_001018116.2	c.-57G>A		5_prime_UTR_variant	1/2	ENST00000307584.6
CAVIN4	XM_047423346.1	c.22-102G>A		intron_variant
CAVIN4	XM_047423347.1	c.21+1132G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAVIN4	ENST00000307584.6	c.-57G>A		5_prime_UTR_variant	1/2	1	NM_001018116.2	P1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56861 AN: 151890 Hom.: 11226 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.0909

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.409

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.387

GnomAD4 exome AF: 0.401 AC: 576776 AN: 1437790 Hom.: 119303 Cov.: 26 AF XY: 0.399 AC XY: 286052 AN XY: 716674

Gnomad4 AFR exome AF: 0.292

Gnomad4 AMR exome AF: 0.515

Gnomad4 ASJ exome AF: 0.430

Gnomad4 EAS exome AF: 0.0739

Gnomad4 SAS exome AF: 0.340

Gnomad4 FIN exome AF: 0.403

Gnomad4 NFE exome AF: 0.417

Gnomad4 OTH exome AF: 0.384

GnomAD4 genome AF: 0.374 AC: 56923 AN: 152008 Hom.: 11237 Cov.: 32 AF XY: 0.375 AC XY: 27827 AN XY: 74292

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.433

Gnomad4 EAS AF: 0.0909

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.409

Gnomad4 NFE AF: 0.418

Gnomad4 OTH AF: 0.385

Alfa AF: 0.410 Hom.: 5019

Bravo AF: 0.372

Asia WGS AF: 0.214 AC: 746 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2018

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	-0.50
Cadd	Benign	13
Dann	Benign	0.90

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: rs1226590; hg19: chr9-103340369;