Variant chr20-20052354-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000377340.6(CRNKL1):c.472A>G(p.Thr158Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.484 in 1,613,646 control chromosomes in the GnomAD database, including 190,825 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.48 ( 18129 hom., cov: 33)

Exomes 𝑓: 0.48 ( 172696 hom. )

Consequence

CRNKL1
ENST00000377340.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.818

Variant links:

Genes affected

CRNKL1 (HGNC:15762): (crooked neck pre-mRNA splicing factor 1) The crooked neck (crn) gene of Drosophila is essential for embryogenesis and is thought to be involved in cell cycle progression and pre-mRNA splicing. A protein encoded by this human locus has been found to localize to pre-mRNA splicing complexes in the nucleus and is necessary for pre-mRNA splicing. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jul 2013]

CRNKL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.8984517E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRNKL1	NM_001278628.2 linkuse as main transcript	c.-12A>G		5_prime_UTR_variant	1/14	ENST00000536226.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRNKL1	ENST00000536226.2 linkuse as main transcript	c.-12A>G		5_prime_UTR_variant	1/14	1	NM_001278628.2	P1	Q9BZJ0-2

Frequencies

GnomAD3 genomes

AF:

0.484

AC:

73616

AN:

151996

Hom.:

18111

Cov.:

show subpopulations

Gnomad AFR

AF:

0.436

Gnomad AMI

AF:

0.693

Gnomad AMR

AF:

0.525

Gnomad ASJ

AF:

0.454

Gnomad EAS

AF:

0.712

Gnomad SAS

AF:

0.485

Gnomad FIN

AF:

0.554

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.476

Gnomad OTH

AF:

0.461

GnomAD3 exomes

AF:

0.513

AC:

128806

AN:

250868

Hom.:

33849

AF XY:

0.506

AC XY:

68723

AN XY:

135714

show subpopulations

Gnomad AFR exome

AF:

0.434

Gnomad AMR exome

AF:

0.587

Gnomad ASJ exome

AF:

0.463

Gnomad EAS exome

AF:

0.731

Gnomad SAS exome

AF:

0.473

Gnomad FIN exome

AF:

0.554

Gnomad NFE exome

AF:

0.476

Gnomad OTH exome

AF:

0.502

GnomAD4 exome

AF:

0.484

AC:

707382

AN:

1461532

Hom.:

172696

Cov.:

AF XY:

0.483

AC XY:

351355

AN XY:

727090

show subpopulations

Gnomad4 AFR exome

AF:

0.438

Gnomad4 AMR exome

AF:

0.581

Gnomad4 ASJ exome

AF:

0.470

Gnomad4 EAS exome

AF:

0.666

Gnomad4 SAS exome

AF:

0.476

Gnomad4 FIN exome

AF:

0.545

Gnomad4 NFE exome

AF:

0.473

Gnomad4 OTH exome

AF:

0.487

GnomAD4 genome

AF:

0.484

AC:

73687

AN:

152114

Hom.:

18129

Cov.:

AF XY:

0.486

AC XY:

36115

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.436

Gnomad4 AMR

AF:

0.525

Gnomad4 ASJ

AF:

0.454

Gnomad4 EAS

AF:

0.712

Gnomad4 SAS

AF:

0.487

Gnomad4 FIN

AF:

0.554

Gnomad4 NFE

AF:

0.476

Gnomad4 OTH

AF:

0.461

Alfa

AF:

0.480

Hom.:

41628

Bravo

AF:

0.485

TwinsUK

AF:

0.486

AC:

1801

ALSPAC

AF:

0.482

AC:

1856

ESP6500AA

AF:

0.441

AC:

1944

ESP6500EA

AF:

0.475

AC:

4087

ExAC

AF:

0.509

AC:

61772

Asia WGS

AF:

0.551

AC:

1918

AN:

3478

EpiCase

AF:

0.468

EpiControl

AF:

0.479

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.81

CADD

Benign

8.2

DANN

Benign

0.75

DEOGEN2

Benign

0.0073

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0016

LIST_S2

Benign

0.13

T;T

MetaRNN

Benign

0.0000019

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.69

.;N

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.42

PROVEAN

Benign

0.28

N;N

REVEL

Benign

0.020

Sift

Benign

1.0

T;T

Sift4G

Benign

0.53

T;T

Polyphen

0.0

B;B

Vest4

0.035

MPC

0.27

ClinPred

0.00057

GERP RS

-0.47

Varity_R

0.031

gMVP

0.097

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over