22-20923183-A-G

Position:

• chr22-20923183-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000354336.8(CRKL):​c.311+4938A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 151,994 control chromosomes in the GnomAD database, including 44,288 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.76 (44288 hom., cov: 31)
• Consequence: CRKL ENST00000354336.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRKL	NM_005207.4	c.311+4938A>G		intron_variant		ENST00000354336.8	NP_005198.1
CRKL	NR_156180.2	n.839+4938A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRKL	ENST00000354336.8	c.311+4938A>G		intron_variant		1	NM_005207.4	ENSP00000346300	P1
CRKL	ENST00000411769.1	c.311+4938A>G		intron_variant, NMD_transcript_variant		1		ENSP00000396646

Frequencies

GnomAD3 genomes AF: 0.759 AC: 115250 AN: 151876 Hom.: 44261 Cov.: 31

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.698

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.693

Gnomad EAS AF: 0.863

Gnomad SAS AF: 0.910

Gnomad FIN AF: 0.879

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.793

Gnomad OTH AF: 0.739

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.759 AC: 115330 AN: 151994 Hom.: 44288 Cov.: 31 AF XY: 0.765 AC XY: 56842 AN XY: 74314

Gnomad4 AFR AF: 0.640

Gnomad4 AMR AF: 0.788

Gnomad4 ASJ AF: 0.693

Gnomad4 EAS AF: 0.863

Gnomad4 SAS AF: 0.910

Gnomad4 FIN AF: 0.879

Gnomad4 NFE AF: 0.793

Gnomad4 OTH AF: 0.742

Alfa AF: 0.770 Hom.: 8627

Bravo AF: 0.744

Asia WGS AF: 0.898 AC: 3122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.6
DANN	Benign	0.68

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

Other links and lift over

dbSNP: rs5761368; hg19: chr22-21277471;