Genetic Variant NM_001393381.1:c.296C>T (chr4-56310676-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001393381.1(CRACD):c.296C>T(p.Thr99Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000176 in 1,610,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

CRACD
NM_001393381.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.53

Publications

0 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:

LOC124900707 (HGNC:):

LOC124900707 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08644408).

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.296C>T	p.Thr99Met	missense	Exon 6 of 11	NP_001380310.1	Q6ZU35
CRACD	NM_001393382.1		c.296C>T	p.Thr99Met	missense	Exon 5 of 10	NP_001380311.1	Q6ZU35
CRACD	NM_020722.2		c.296C>T	p.Thr99Met	missense	Exon 6 of 11	NP_065773.1	Q6ZU35

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CRACD	ENST00000682029.1	MANE Select	c.296C>T	p.Thr99Met	missense	Exon 6 of 11	ENSP00000507165.1	Q6ZU35
CRACD	ENST00000541073.5	TSL:1	c.275C>T	p.Thr92Met	missense	Exon 5 of 10	ENSP00000444006.1	F5H1N7
CRACD	ENST00000505410.1	TSL:1	n.192C>T		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes

AF:

0.0000921

AC:

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000104

AC:

AN:

249534

AF XY:

0.0000812

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.000330

GnomAD4 exome

AF:

0.000185

AC:

270

AN:

1457992

Hom.:

Cov.:

AF XY:

0.000163

AC XY:

118

AN XY:

725584

show subpopulations

African (AFR)

AF:

0.000270

AC:

AN:

33380

American (AMR)

AF:

0.000447

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26112

East Asian (EAS)

AF:

0.00

AC:

AN:

39666

South Asian (SAS)

AF:

0.00

AC:

AN:

86174

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000208

AC:

231

AN:

1108494

Other (OTH)

AF:

0.000166

AC:

AN:

60270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.427

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000921

AC:

AN:

152068

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.0000725

AC:

AN:

41398

American (AMR)

AF:

0.000131

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68016

Other (OTH)

AF:

0.000478

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

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:

0.000131

Hom.:

Bravo

AF:

0.000159

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000993

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000119

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

0.083

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.046

Eigen

Benign

-0.040

Eigen_PC

Benign

-0.093

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.72

M_CAP

Benign

0.0083

MetaRNN

Benign

0.086

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.7

PhyloP100

1.5

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.11

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.018

Polyphen

0.94

Vest4

0.21

MVP

0.17

MPC

0.94

ClinPred

0.13

GERP RS

3.9

Varity_R

0.076

gMVP

0.28

Mutation Taster

=97/3

polymorphism

(source)

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

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