dbSNP rs199976955: CRACD:p.Lys37Arg (chr4-56298339-A-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001393381.1(CRACD):c.110A>G(p.Lys37Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000769 in 1,614,042 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00047 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00080 ( 2 hom. )

Consequence

CRACD
NM_001393381.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.14

Publications

2 publications found

Variant links:

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]

CRACD links:

ENSG00000286093 (HGNC:):

ENSG00000286093 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1185309).

BS2

High Homozygotes in GnomAdExome4 at 2 gene

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CRACD	NM_001393381.1	MANE Select	c.110A>G	p.Lys37Arg	missense	Exon 4 of 11	NP_001380310.1	Q6ZU35
CRACD	NM_001393382.1		c.110A>G	p.Lys37Arg	missense	Exon 3 of 10	NP_001380311.1	Q6ZU35
CRACD	NM_020722.2		c.110A>G	p.Lys37Arg	missense	Exon 4 of 11	NP_065773.1	Q6ZU35

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CRACD	ENST00000682029.1	MANE Select	c.110A>G	p.Lys37Arg	missense	Exon 4 of 11	ENSP00000507165.1	Q6ZU35
CRACD	ENST00000541073.5	TSL:1	c.67A>G	p.Lys23Glu	missense	Exon 2 of 10	ENSP00000444006.1	F5H1N7
CRACD	ENST00000646253.2		c.365A>G	p.Lys122Arg	missense	Exon 5 of 12	ENSP00000495373.2	A0A2R8Y6P1

Frequencies

GnomAD3 genomes

AF:

0.000466

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000794

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000505

AC:

126

AN:

249474

AF XY:

0.000517

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.000435

Gnomad ASJ exome

AF:

0.000596

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.000857

Gnomad OTH exome

AF:

0.000661

GnomAD4 exome

AF:

0.000800

AC:

1170

AN:

1461830

Hom.:

Cov.:

AF XY:

0.000747

AC XY:

543

AN XY:

727212

show subpopulations

African (AFR)

AF:

0.0000896

AC:

AN:

33480

American (AMR)

AF:

0.000559

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86226

European-Finnish (FIN)

AF:

0.000243

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000971

AC:

1080

AN:

1111988

Other (OTH)

AF:

0.000646

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

122

184

245

306

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

152

190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000466

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.000498

AC XY:

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

41448

American (AMR)

AF:

0.000458

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000794

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000802

Hom.:

Bravo

AF:

0.000465

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000847

AC:

ExAC

AF:

0.000488

AC:

EpiCase

AF:

0.000872

EpiControl

AF:

0.00101

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.41

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.015

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.47

M_CAP

Benign

0.012

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.0

PhyloP100

6.1

PROVEAN

Benign

0.14

REVEL

Benign

0.12

Sift

Pathogenic

0.0

Sift4G

Benign

0.37

Polyphen

0.97

Vest4

0.45

MVP

0.29

ClinPred

0.046

GERP RS

5.3

Varity_R

0.16

Mutation Taster

=86/14

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over