rs2255255

Variant names:

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 1P and 12B. PP2BP4_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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

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

Publications

37 publications found

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:

CFAP61 (HGNC:15872): (cilia and flagella associated protein 61) Predicted to be involved in cilium movement and cilium organization. Predicted to be located in axoneme and motile cilium. Predicted to colocalize with radial spoke stalk. [provided by Alliance of Genome Resources, Apr 2022]

CFAP61 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 0.87994 (below the threshold of 3.09). Trascript score misZ: 1.501 (below the threshold of 3.09).

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000377340.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CRNKL1	NM_001278628.2	MANE Select	c.-12A>G		5_prime_UTR	Exon 1 of 14	NP_001265557.1
CRNKL1	NM_016652.6		c.472A>G	p.Thr158Ala	missense	Exon 2 of 15	NP_057736.4
CRNKL1	NM_001278625.2		c.436A>G	p.Thr146Ala	missense	Exon 2 of 15	NP_001265554.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CRNKL1	ENST00000377340.6	TSL:1	c.472A>G	p.Thr158Ala	missense	Exon 2 of 15	ENSP00000366557.2
CRNKL1	ENST00000377327.8	TSL:1	c.436A>G	p.Thr146Ala	missense	Exon 2 of 15	ENSP00000366544.4
CRNKL1	ENST00000536226.2	TSL:1 MANE Select	c.-12A>G		5_prime_UTR	Exon 1 of 14	ENSP00000440733.1

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

GnomAD2 exomes

AF:

0.513

AC:

128806

AN:

250868

AF XY:

0.506

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 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

African (AFR)

AF:

0.438

AC:

14668

AN:

33480

American (AMR)

AF:

0.581

AC:

25981

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.470

AC:

12297

AN:

26136

East Asian (EAS)

AF:

0.666

AC:

26422

AN:

39698

South Asian (SAS)

AF:

0.476

AC:

41090

AN:

86256

European-Finnish (FIN)

AF:

0.545

AC:

28978

AN:

53160

Middle Eastern (MID)

AF:

0.491

AC:

2829

AN:

5766

European-Non Finnish (NFE)

AF:

0.473

AC:

525702

AN:

1111934

Other (OTH)

AF:

0.487

AC:

29415

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

23316

46632

69947

93263

116579

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15736

31472

47208

62944

78680

<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:

0.484

AC:

73687

AN:

152114

Hom.:

18129

Cov.:

AF XY:

0.486

AC XY:

36115

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.436

AC:

18114

AN:

41502

American (AMR)

AF:

0.525

AC:

8024

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.454

AC:

1577

AN:

3470

East Asian (EAS)

AF:

0.712

AC:

3671

AN:

5156

South Asian (SAS)

AF:

0.487

AC:

2349

AN:

4824

European-Finnish (FIN)

AF:

0.554

AC:

5862

AN:

10584

Middle Eastern (MID)

AF:

0.439

AC:

129

AN:

294

European-Non Finnish (NFE)

AF:

0.476

AC:

32355

AN:

67974

Other (OTH)

AF:

0.461

AC:

974

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

2012

4023

6035

8046

10058

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

674

1348

2022

2696

3370

<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:

0.479

Hom.:

57255

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 v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.81

CADD

Benign

8.2

(source)

DANN

Benign

0.75

DEOGEN2

Benign

0.0073

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0016

LIST_S2

Benign

0.13

MetaRNN

Benign

0.0000019

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.69

PhyloP100

-0.82

PrimateAI

Benign

0.42

PROVEAN

Benign

0.28

REVEL

Benign

0.020

Sift

Benign

1.0

Sift4G

Benign

0.53

Polyphen

0.0

Vest4

0.035

MPC

0.27

ClinPred

0.00057

GERP RS

-0.47

PromoterAI

-0.049

Neutral

(source)

Varity_R

0.031

gMVP

0.097

Mutation Taster

=100/0

polymorphism (auto)

(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