Variant 1-26183819-AC-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_006314.3(CNKSR1):c.851del(p.Pro284HisfsTer74) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0561 in 1,335,818 control chromosomes in the GnomAD database, including 2,058 homozygotes. Variant has been reported in ClinVar as Benign (★★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.034 ( 101 hom., cov: 28)

Exomes 𝑓: 0.058 ( 1957 hom. )

Consequence

CNKSR1
NM_006314.3 frameshift

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.256

Variant links:

Genes affected

CNKSR1 (HGNC:19700): (connector enhancer of kinase suppressor of Ras 1) This gene encodes a protein containing several motifs involved in protein-protein interaction, including PDZ, PH (Pleckstrin homology), and SAM (sterile alpha motif) domains. The encoded protein acts as a scaffold component for receptor tyrosine kinase signaling and may mediate crosstalk between different signaling pathways. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

CNKSR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 1-26183819-AC-A is Benign according to our data. Variant chr1-26183819-AC-A is described in ClinVar as [Benign]. Clinvar id is 252663.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.055 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CNKSR1	NM_006314.3 linkuse as main transcript	c.851del	p.Pro284HisfsTer74	frameshift_variant	9/21	ENST00000361530.11	NP_006305.2
CNKSR1	NM_001297647.2 linkuse as main transcript	c.872del	p.Pro291HisfsTer74	frameshift_variant	9/21		NP_001284576.1
CNKSR1	NM_001297648.2 linkuse as main transcript	c.77del	p.Pro26HisfsTer74	frameshift_variant	9/21		NP_001284577.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNKSR1	ENST00000361530.11 linkuse as main transcript	c.851del	p.Pro284HisfsTer74	frameshift_variant	9/21	1	NM_006314.3	ENSP00000354609	P1	Q969H4-2

Frequencies

GnomAD3 genomes

AF:

0.0344

AC:

4146

AN:

120542

Hom.:

101

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00865

Gnomad AMI

AF:

0.0187

Gnomad AMR

AF:

0.0170

Gnomad ASJ

AF:

0.0167

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0131

Gnomad FIN

AF:

0.0368

Gnomad MID

AF:

0.00376

Gnomad NFE

AF:

0.0567

Gnomad OTH

AF:

0.0274

GnomAD3 exomes

AF:

0.0332

AC:

8223

AN:

247884

Hom.:

211

AF XY:

0.0334

AC XY:

4498

AN XY:

134606

show subpopulations

Gnomad AFR exome

AF:

0.00819

Gnomad AMR exome

AF:

0.0124

Gnomad ASJ exome

AF:

0.0186

Gnomad EAS exome

AF:

0.0000547

Gnomad SAS exome

AF:

0.0109

Gnomad FIN exome

AF:

0.0409

Gnomad NFE exome

AF:

0.0544

Gnomad OTH exome

AF:

0.0393

GnomAD4 exome

AF:

0.0582

AC:

70784

AN:

1215220

Hom.:

1957

Cov.:

AF XY:

0.0566

AC XY:

34315

AN XY:

606542

show subpopulations

Gnomad4 AFR exome

AF:

0.00923

Gnomad4 AMR exome

AF:

0.0159

Gnomad4 ASJ exome

AF:

0.0274

Gnomad4 EAS exome

AF:

0.000147

Gnomad4 SAS exome

AF:

0.0121

Gnomad4 FIN exome

AF:

0.0556

Gnomad4 NFE exome

AF:

0.0676

Gnomad4 OTH exome

AF:

0.0587

GnomAD4 genome

AF:

0.0344

AC:

4145

AN:

120598

Hom.:

101

Cov.:

AF XY:

0.0316

AC XY:

1826

AN XY:

57768

show subpopulations

Gnomad4 AFR

AF:

0.00864

Gnomad4 AMR

AF:

0.0169

Gnomad4 ASJ

AF:

0.0167

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0131

Gnomad4 FIN

AF:

0.0368

Gnomad4 NFE

AF:

0.0567

Gnomad4 OTH

AF:

0.0272

Alfa

AF:

0.00546

Hom.:

EpiCase

AF:

0.0461

EpiControl

AF:

0.0460

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Oct 16, 2015

- -

Usher syndrome type 2C

Benign:1

Benign, criteria provided, single submitter

research

Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard

The homozygous c.851delC variant in CNKSR1 has been identified in an individual with intellectual disability in the literature (PMID: 21937992). However, this variant is classified as benign for autosomal recessive intellectual disability because it has been identified in >5% of European (non-Finnish) chromosomes and 108 total homozygotes, by ExAC (http://gnomad.broadinstitute.org/). -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 06, 2018

This variant is associated with the following publications: (PMID: 30450701, 27535533, 21937992) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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