Variant 20-20052678-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_016652.6(CRNKL1):c.148C>T(p.Gln50*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00693 in 1,612,988 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0050 ( 7 hom., cov: 34)

Exomes 𝑓: 0.0071 ( 47 hom. )

Consequence

CRNKL1
NM_016652.6 stop_gained

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0810

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:

CFAP61 (HGNC:):

CFAP61 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 20-20052678-G-A is Benign according to our data. Variant chr20-20052678-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2652228.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 763 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CFAP61	NM_015585.4 linkuse as main transcript	c.-37+87G>A		intron_variant		ENST00000245957.10	NP_056400.3	Q8NHU2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CFAP61	ENST00000245957.10 linkuse as main transcript	c.-37+87G>A		intron_variant		1	NM_015585.4	ENSP00000245957.5		Q8NHU2-1

Frequencies

GnomAD3 genomes

AF:

0.00500

AC:

762

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00154

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.00490

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00855

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.00478

AC:

1184

AN:

247716

Hom.:

AF XY:

0.00487

AC XY:

656

AN XY:

134682

show subpopulations

Gnomad AFR exome

AF:

0.00153

Gnomad AMR exome

AF:

0.00308

Gnomad ASJ exome

AF:

0.00171

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00170

Gnomad FIN exome

AF:

0.000945

Gnomad NFE exome

AF:

0.00831

Gnomad OTH exome

AF:

0.00611

GnomAD4 exome

AF:

0.00713

AC:

10418

AN:

1460622

Hom.:

Cov.:

AF XY:

0.00700

AC XY:

5088

AN XY:

726594

show subpopulations

Gnomad4 AFR exome

AF:

0.00105

Gnomad4 AMR exome

AF:

0.00325

Gnomad4 ASJ exome

AF:

0.00253

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00145

Gnomad4 FIN exome

AF:

0.00116

Gnomad4 NFE exome

AF:

0.00864

Gnomad4 OTH exome

AF:

0.00540

GnomAD4 genome

AF:

0.00501

AC:

763

AN:

152366

Hom.:

Cov.:

AF XY:

0.00479

AC XY:

357

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.00154

Gnomad4 AMR

AF:

0.00490

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00855

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00771

Hom.:

Bravo

AF:

0.00525

TwinsUK

AF:

0.00998

AC:

ALSPAC

AF:

0.00882

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00804

AC:

ExAC

AF:

0.00475

AC:

576

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00785

EpiControl

AF:

0.00771

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2023

CFAP61: BS2; CRNKL1: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Uncertain

0.030

CADD

Benign

7.7

DANN

Uncertain

0.99

Eigen

Uncertain

0.28

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.013

Vest4

0.036

GERP RS

2.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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