22-20918024-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_005207.4(CRKL):​c.90C>T​(p.Gly30Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000219 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

CRKL
NM_005207.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0740
Variant links:
Genes affected
CRKL (HGNC:2363): (CRK like proto-oncogene, adaptor protein) This gene encodes a protein kinase containing SH2 and SH3 (src homology) domains which has been shown to activate the RAS and JUN kinase signaling pathways and transform fibroblasts in a RAS-dependent fashion. It is a substrate of the BCR-ABL tyrosine kinase, plays a role in fibroblast transformation by BCR-ABL, and may be oncogenic.[provided by RefSeq, Jan 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.27).
BP6
Variant 22-20918024-C-T is Benign according to our data. Variant chr22-20918024-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1907994.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.074 with no splicing effect.
BS2
High AC in GnomAdExome4 at 32 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CRKLNM_005207.4 linkc.90C>T p.Gly30Gly synonymous_variant Exon 1 of 3 ENST00000354336.8 NP_005198.1 P46109
CRKLNR_156180.2 linkn.618C>T non_coding_transcript_exon_variant Exon 1 of 4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CRKLENST00000354336.8 linkc.90C>T p.Gly30Gly synonymous_variant Exon 1 of 3 1 NM_005207.4 ENSP00000346300.3 P46109
CRKLENST00000411769.1 linkn.90C>T non_coding_transcript_exon_variant Exon 1 of 4 1 ENSP00000396646.1 P46109

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.0000219
AC:
32
AN:
1461880
Hom.:
0
Cov.:
31
AF XY:
0.0000289
AC XY:
21
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000279
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000795
Hom.:
0

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Jul 30, 2022
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.27
CADD
Benign
14
DANN
Benign
0.95
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.8

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.

Other links and lift over

dbSNP: rs1929754451; hg19: chr22-21272312; COSMIC: COSV100574206; API