Variant 4-56314308-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001393381.1(CRACD):c.806T>G(p.Leu269Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000828 in 1,552,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L269I) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00088 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00082 ( 0 hom. )

Consequence

CRACD
NM_001393381.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.512

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0053319037).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRACD	NM_001393381.1 linkuse as main transcript	c.806T>G	p.Leu269Arg	missense_variant	8/11	ENST00000682029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRACD	ENST00000682029.1 linkuse as main transcript	c.806T>G	p.Leu269Arg	missense_variant	8/11		NM_001393381.1	A2

Frequencies

GnomAD3 genomes

AF:

0.000878

AC:

133

AN:

151480

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000510

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.00223

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000568

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000766

Gnomad OTH

AF:

0.00288

GnomAD3 exomes

AF:

0.00111

AC:

172

AN:

155244

Hom.:

AF XY:

0.000970

AC XY:

AN XY:

82460

show subpopulations

Gnomad AFR exome

AF:

0.000613

Gnomad AMR exome

AF:

0.00287

Gnomad ASJ exome

AF:

0.000590

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000697

Gnomad FIN exome

AF:

0.000517

Gnomad NFE exome

AF:

0.00107

Gnomad OTH exome

AF:

0.000684

GnomAD4 exome

AF:

0.000822

AC:

1152

AN:

1400836

Hom.:

Cov.:

AF XY:

0.000819

AC XY:

566

AN XY:

691124

show subpopulations

Gnomad4 AFR exome

AF:

0.000440

Gnomad4 AMR exome

AF:

0.00260

Gnomad4 ASJ exome

AF:

0.000675

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000504

Gnomad4 FIN exome

AF:

0.000628

Gnomad4 NFE exome

AF:

0.000829

Gnomad4 OTH exome

AF:

0.00105

GnomAD4 genome

AF:

0.000877

AC:

133

AN:

151598

Hom.:

Cov.:

AF XY:

0.000864

AC XY:

AN XY:

74080

show subpopulations

Gnomad4 AFR

AF:

0.000509

Gnomad4 AMR

AF:

0.00223

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000568

Gnomad4 NFE

AF:

0.000766

Gnomad4 OTH

AF:

0.00285

Alfa

AF:

0.000818

Hom.:

Bravo

AF:

0.00108

ExAC

AF:

0.000467

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 27, 2022

The c.806T>G (p.L269R) alteration is located in exon 8 (coding exon 5) of the KIAA1211 gene. This alteration results from a T to G substitution at nucleotide position 806, causing the leucine (L) at amino acid position 269 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.52

Cadd

Benign

Dann

Benign

0.95

Eigen

Benign

0.16

Eigen_PC

Benign

0.12

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.56

T;T;.;T;T

M_CAP

Benign

0.0068

MetaRNN

Benign

0.0053

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.48

Polyphen

1.0

.;.;D;D;D

Vest4

0.40, 0.39, 0.58

MVP

0.36

MPC

0.40

ClinPred

0.014

GERP RS

4.8

Varity_R

0.29

gMVP

0.27

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over