Variant 1-26181848-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006314.3(CNKSR1):c.393-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00312 in 1,613,830 control chromosomes in the GnomAD database, including 110 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 48 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 62 hom. )

Consequence

CNKSR1
NM_006314.3 intron

Scores

Splicing: ADA: 0.0001720

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.223

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:

CNKSR1 (HGNC:):

CNKSR1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 1-26181848-C-T is Benign according to our data. Variant chr1-26181848-C-T is described in ClinVar as [Benign]. Clinvar id is 790480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
CNKSR1	NM_006314.3 linkuse as main transcript	c.393-9C>T	intron_variant	ENST00000361530.11	NP_006305.2	Q969H4-2Q53GM7
CNKSR1	NM_001297647.2 linkuse as main transcript	c.393-9C>T	intron_variant		NP_001284576.1	Q969H4-1B4DL25
CNKSR1	NM_001297648.2 linkuse as main transcript	c.-377-9C>T	intron_variant		NP_001284577.1	Q969H4G3V160B4DL25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNKSR1	ENST00000361530.11 linkuse as main transcript	c.393-9C>T		intron_variant		1	NM_006314.3	ENSP00000354609.6		Q969H4-2

Frequencies

GnomAD3 genomes

AF:

0.0162

AC:

2463

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0538

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000632

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.00420

AC:

1057

AN:

251410

Hom.:

AF XY:

0.00319

AC XY:

433

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.0518

Gnomad AMR exome

AF:

0.00413

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000501

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00176

AC:

2568

AN:

1461562

Hom.:

Cov.:

AF XY:

0.00146

AC XY:

1065

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.0518

Gnomad4 AMR exome

AF:

0.00467

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000186

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000257

Gnomad4 OTH exome

AF:

0.00494

GnomAD4 genome

AF:

0.0162

AC:

2468

AN:

152268

Hom.:

Cov.:

AF XY:

0.0163

AC XY:

1215

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0538

Gnomad4 AMR

AF:

0.0105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000632

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.00685

Hom.:

Bravo

AF:

0.0188

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.000927

EpiControl

AF:

0.000889

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

8.0

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00017

dbscSNV1_RF

Benign

0.0040

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