4-56298287-A-G

Variant names:

• chr4-56298287-A-G
• rs1458397805
• NM_001393381.1:c.58A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001393381.1(CRACD):​c.58A>G​(p.Ser20Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CRACD NM_001393381.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.06
• Publications: 0 publications found

Genes affected

CRACD (HGNC:29219): (capping protein inhibiting regulator of actin dynamics) Involved in negative regulation of barbed-end actin filament capping. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000286093 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20622599).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393381.1. 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
	CRACD	NM_001393381.1	MANE Select	c.58A>G	p.Ser20Gly	missense	Exon 4 of 11	NP_001380310.1	Q6ZU35
	CRACD	NM_001393382.1		c.58A>G	p.Ser20Gly	missense	Exon 3 of 10	NP_001380311.1	Q6ZU35
	CRACD	NM_020722.2		c.58A>G	p.Ser20Gly	missense	Exon 4 of 11	NP_065773.1	Q6ZU35

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRACD	ENST00000682029.1	MANE Select	c.58A>G	p.Ser20Gly	missense	Exon 4 of 11	ENSP00000507165.1	Q6ZU35
	CRACD	ENST00000541073.5	TSL:1	c.15A>G	p.Lys5Lys	synonymous	Exon 2 of 10	ENSP00000444006.1	F5H1N7
	CRACD	ENST00000646253.2		c.313A>G	p.Ser105Gly	missense	Exon 5 of 12	ENSP00000495373.2	A0A2R8Y6P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461852 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727226

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111996

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.066	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	0.76	N
PhyloP100		3.1
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.059
Sift	Benign	0.046	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.37
MutPred		0.15		Gain of sheet (P = 0.0266)
MVP		0.36
MPC		0.88
ClinPred		0.82	D
GERP RS		5.2
Varity_R		0.12
gMVP		0.065
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1458397805; hg19: chr4-57164453;