Variant 4-56314313-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001393381.1(CRACD):c.811G>C(p.Glu271Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000457 in 1,552,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

CRACD
NM_001393381.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.00

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.103477).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRACD	NM_001393381.1 linkuse as main transcript	c.811G>C	p.Glu271Gln	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.811G>C	p.Glu271Gln	missense_variant	8/11		NM_001393381.1	A2

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000713

AC:

AN:

154290

Hom.:

AF XY:

0.0000732

AC XY:

AN XY:

81934

show subpopulations

Gnomad AFR exome

AF:

0.000125

Gnomad AMR exome

AF:

0.000243

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000506

Gnomad OTH exome

AF:

0.000230

GnomAD4 exome

AF:

0.0000464

AC:

AN:

1399936

Hom.:

Cov.:

AF XY:

0.0000492

AC XY:

AN XY:

690636

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000196

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000528

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000226

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.0000203

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 29, 2022

The c.811G>C (p.E271Q) alteration is located in exon 8 (coding exon 5) of the KIAA1211 gene. This alteration results from a G to C substitution at nucleotide position 811, causing the glutamic acid (E) at amino acid position 271 to be replaced by a glutamine (Q). 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

0.11

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.56

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.75

T;T;.;T;T

M_CAP

Benign

0.0023

MetaRNN

Benign

0.10

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.78

N;N;N

PrimateAI

Benign

0.45

Polyphen

0.95

.;.;P;P;P

Vest4

0.13, 0.16, 0.16

MutPred

0.11

.;Gain of MoRF binding (P = 0.0985);Gain of MoRF binding (P = 0.0985);Gain of MoRF binding (P = 0.0985);.;

MVP

0.45

MPC

0.27

ClinPred

0.13

GERP RS

3.4

Varity_R

0.12

gMVP

0.079

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