chr9-100585926-A-T

Variant names:

• chr9-100585926-A-T
• rs28623148
• NM_001018116.2:c.570A>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001018116.2(CAVIN4):​c.570A>T​(p.Ser190Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.039 in 1,614,118 control chromosomes in the GnomAD database, including 3,269 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.043 (305 hom., cov: 32)
  • Exomes 𝑓: 0.039 (2964 hom.)
• Consequence: CAVIN4 NM_001018116.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.468
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 9-100585926-A-T is Benign according to our data. Variant chr9-100585926-A-T is described in ClinVar as Benign. ClinVar VariationId is 226741.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.468 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.194 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAVIN4	NM_001018116.2	MANE Select	c.570A>T	p.Ser190Ser	synonymous	Exon 2 of 2	NP_001018126.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAVIN4	ENST00000307584.6	TSL:1 MANE Select	c.570A>T	p.Ser190Ser	synonymous	Exon 2 of 2	ENSP00000418668.1
	CAVIN4	ENST00000956994.1		c.567A>T	p.Ser189Ser	synonymous	Exon 2 of 2	ENSP00000627053.1

Frequencies

GnomAD3 genomes AF: 0.0434 AC: 6610 AN: 152134 Hom.: 307 Cov.: 32

Gnomad AFR AF: 0.0548

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0327

Gnomad ASJ AF: 0.0233

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.00989

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0221

Gnomad OTH AF: 0.0426

GnomAD2 exomes AF: 0.0605 AC: 15184 AN: 251174 AF XY: 0.0655

Gnomad AFR exome AF: 0.0543

Gnomad AMR exome AF: 0.0338

Gnomad ASJ exome AF: 0.0220

Gnomad EAS exome AF: 0.215

Gnomad FIN exome AF: 0.0109

Gnomad NFE exome AF: 0.0237

Gnomad OTH exome AF: 0.0395

GnomAD4 exome AF: 0.0385 AC: 56339 AN: 1461866 Hom.: 2964 Cov.: 33 AF XY: 0.0425 AC XY: 30911 AN XY: 727230

African (AFR) AF: 0.0522 AC: 1747 AN: 33480

American (AMR) AF: 0.0352 AC: 1576 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0212 AC: 555 AN: 26136

East Asian (EAS) AF: 0.197 AC: 7819 AN: 39700

South Asian (SAS) AF: 0.183 AC: 15751 AN: 86258

European-Finnish (FIN) AF: 0.0121 AC: 644 AN: 53416

Middle Eastern (MID) AF: 0.0317 AC: 183 AN: 5768

European-Non Finnish (NFE) AF: 0.0227 AC: 25290 AN: 1111988

Other (OTH) AF: 0.0459 AC: 2774 AN: 60396

GnomAD4 genome AF: 0.0434 AC: 6601 AN: 152252 Hom.: 305 Cov.: 32 AF XY: 0.0460 AC XY: 3423 AN XY: 74454

African (AFR) AF: 0.0547 AC: 2273 AN: 41548

American (AMR) AF: 0.0326 AC: 498 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0233 AC: 81 AN: 3470

East Asian (EAS) AF: 0.203 AC: 1047 AN: 5162

South Asian (SAS) AF: 0.204 AC: 984 AN: 4818

European-Finnish (FIN) AF: 0.00989 AC: 105 AN: 10620

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0221 AC: 1505 AN: 68020

Other (OTH) AF: 0.0427 AC: 90 AN: 2110

Alfa AF: 0.0256 Hom.: 20

Bravo AF: 0.0428

Asia WGS AF: 0.212 AC: 737 AN: 3478

EpiCase AF: 0.0230

EpiControl AF: 0.0213

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	7.8
DANN	Benign	0.76
PhyloP100		0.47
Mutation Taster		=100/0	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: rs28623148; hg19: chr9-103348208; COSMIC: COSV56867371; COSMIC: COSV56867371;