chr9-100578087-G-A

Variant names:

• chr9-100578087-G-A
• rs1226590
• NM_001018116.2:c.-57G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.58
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -20 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 VariationId is 674700.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001018116.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAVIN4	NM_001018116.2	MANE Select	c.-57G>A		5_prime_UTR	Exon 1 of 2	NP_001018126.1	Q5BKX8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAVIN4	ENST00000307584.6	TSL:1 MANE Select	c.-57G>A		5_prime_UTR	Exon 1 of 2	ENSP00000418668.1	Q5BKX8
	CAVIN4	ENST00000956994.1		c.-57G>A		5_prime_UTR	Exon 1 of 2	ENSP00000627053.1

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

African (AFR) AF: 0.292 AC: 9638 AN: 32964

American (AMR) AF: 0.515 AC: 22871 AN: 44386

Ashkenazi Jewish (ASJ) AF: 0.430 AC: 11130 AN: 25904

East Asian (EAS) AF: 0.0739 AC: 2918 AN: 39482

South Asian (SAS) AF: 0.340 AC: 28836 AN: 84912

European-Finnish (FIN) AF: 0.403 AC: 20273 AN: 50300

Middle Eastern (MID) AF: 0.336 AC: 1923 AN: 5720

European-Non Finnish (NFE) AF: 0.417 AC: 456304 AN: 1094534

Other (OTH) AF: 0.384 AC: 22883 AN: 59588

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

African (AFR) AF: 0.299 AC: 12397 AN: 41462

American (AMR) AF: 0.453 AC: 6910 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 1501 AN: 3470

East Asian (EAS) AF: 0.0909 AC: 470 AN: 5168

South Asian (SAS) AF: 0.331 AC: 1594 AN: 4822

European-Finnish (FIN) AF: 0.409 AC: 4319 AN: 10550

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.418 AC: 28385 AN: 67958

Other (OTH) AF: 0.385 AC: 810 AN: 2106

Alfa AF: 0.407 Hom.: 5997

Bravo AF: 0.372

Asia WGS AF: 0.214 AC: 746 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	13
DANN	Benign	0.90
PhyloP100		2.6
PromoterAI		-0.0058	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1226590; hg19: chr9-103340369; COSMIC: COSV108145224; COSMIC: COSV108145224;