rs137921742

Variant names:

• chr9-100578535-G-A
• rs137921742
• NM_001018116.2:c.392G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-100578535-G-A
• chr9-100578535-G-T

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.392G>A​(p.Arg131His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00363 in 1,613,196 control chromosomes in the GnomAD database, including 320 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0081 (67 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (253 hom.)
• Consequence: CAVIN4 NM_001018116.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 9.92
• Publications: 3 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 (MetaRNN=0.006243199).
• BP6: Variant 9-100578535-G-A is Benign according to our data. Variant chr9-100578535-G-A is described in ClinVar as Benign. ClinVar VariationId is 226738.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.071 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.392G>A	p.Arg131His	missense	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.392G>A	p.Arg131His	missense	Exon 1 of 2	ENSP00000418668.1	Q5BKX8
	CAVIN4	ENST00000956994.1		c.392G>A	p.Arg131His	missense	Exon 1 of 2	ENSP00000627053.1

Frequencies

GnomAD3 genomes AF: 0.00808 AC: 1230 AN: 152158 Hom.: 66 Cov.: 32

Gnomad AFR AF: 0.00150

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0744

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00908

GnomAD2 exomes AF: 0.0146 AC: 3569 AN: 244484 AF XY: 0.0107

Gnomad AFR exome AF: 0.00151

Gnomad AMR exome AF: 0.101

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.000101

Gnomad OTH exome AF: 0.00969

GnomAD4 exome AF: 0.00316 AC: 4617 AN: 1460920 Hom.: 253 Cov.: 33 AF XY: 0.00260 AC XY: 1887 AN XY: 726722

African (AFR) AF: 0.00105 AC: 35 AN: 33462

American (AMR) AF: 0.0961 AC: 4297 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26132

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39696

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86244

European-Finnish (FIN) AF: 0.0000760 AC: 4 AN: 52618

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5766

European-Non Finnish (NFE) AF: 0.0000962 AC: 107 AN: 1111920

Other (OTH) AF: 0.00278 AC: 168 AN: 60376

GnomAD4 genome AF: 0.00811 AC: 1235 AN: 152276 Hom.: 67 Cov.: 32 AF XY: 0.00987 AC XY: 735 AN XY: 74458

African (AFR) AF: 0.00149 AC: 62 AN: 41558

American (AMR) AF: 0.0746 AC: 1141 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68014

Other (OTH) AF: 0.00899 AC: 19 AN: 2114

Alfa AF: 0.00155 Hom.: 15

Bravo AF: 0.0126

ESP6500AA AF: 0.00136 AC: 6

ESP6500EA AF: 0.000582 AC: 5

ExAC AF: 0.0100 AC: 1215

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

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
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Pathogenic	0.25
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	T
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.88	D
MetaRNN	Benign	0.0062	T
MetaSVM	Benign	-0.79	T
PhyloP100		9.9
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.5	D
REVEL	Uncertain	0.43
Sift	Benign	0.21	T
Sift4G	Uncertain	0.0050	D
Polyphen		1.0	D
Vest4		0.94
MPC		0.067
ClinPred		0.041	T
GERP RS		5.0
PromoterAI		-0.076	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.39
gMVP		0.28
Mutation Taster		=75/25	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: rs137921742; hg19: chr9-103340817;