rs751703046

Variant names:

• chr9-100586276-G-A
• rs751703046
• NM_001018116.2:c.920G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-100586276-G-A
• chr9-100586276-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001018116.2(CAVIN4):​c.920G>A​(p.Ser307Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,445,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S307T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CAVIN4 NM_001018116.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.034679472).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAVIN4	NM_001018116.2	c.920G>A	p.Ser307Asn	missense_variant	Exon 2 of 2	ENST00000307584.6	NP_001018126.1
CAVIN4	XM_047423346.1	c.896G>A	p.Ser299Asn	missense_variant	Exon 3 of 3		XP_047279302.1
CAVIN4	XM_047423347.1	c.533G>A	p.Ser178Asn	missense_variant	Exon 2 of 2		XP_047279303.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAVIN4	ENST00000307584.6	c.920G>A	p.Ser307Asn	missense_variant	Exon 2 of 2	1	NM_001018116.2	ENSP00000418668.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1445380 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 716860

African (AFR) AF: 0.00 AC: 0 AN: 32898

American (AMR) AF: 0.00 AC: 0 AN: 42590

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25230

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39468

South Asian (SAS) AF: 0.00 AC: 0 AN: 84336

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53120

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5670

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1102500

Other (OTH) AF: 0.00 AC: 0 AN: 59568

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	5.8
DANN	Benign	0.90
DEOGEN2	Benign	0.018	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.079	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.2
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.040
Sift	Benign	0.30	T
Sift4G	Benign	0.28	T
Polyphen		0.0010	B
Vest4		0.035
MutPred		0.14		Loss of phosphorylation at S307 (P = 0.0091);
MVP		0.088
MPC		0.036
ClinPred		0.034	T
GERP RS		0.27
Varity_R		0.039
gMVP		0.044
Mutation Taster		=96/4	polymorphism

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: rs751703046; hg19: chr9-103348558;