chr17-1433113-T-C

Position:

• chr17-1433113-T-C

Variant summary

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

The NM_016823.4(CRK):​c.777+3507A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,082 control chromosomes in the GnomAD database, including 2,043 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 0.14 (2043 hom., cov: 31)
• Consequence: CRK NM_016823.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.44

Genes affected

CRK (HGNC:2362): (CRK proto-oncogene, adaptor protein) This gene encodes a member of an adapter protein family that binds to several tyrosine-phosphorylated proteins. The product of this gene has several SH2 and SH3 domains (src-homology domains) and is involved in several signaling pathways, recruiting cytoplasmic proteins in the vicinity of tyrosine kinase through SH2-phosphotyrosine interaction. The N-terminal SH2 domain of this protein functions as a positive regulator of transformation whereas the C-terminal SH3 domain functions as a negative regulator of transformation. Two alternative transcripts encoding different isoforms with distinct biological activity have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRK	NM_016823.4	c.777+3507A>G		intron_variant		ENST00000300574.3	NP_058431.2
CRK	NM_005206.5	c.607+3677A>G		intron_variant			NP_005197.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRK	ENST00000300574.3	c.777+3507A>G		intron_variant		1	NM_016823.4	ENSP00000300574	P1
CRK	ENST00000398970.5	c.607+3677A>G		intron_variant		1		ENSP00000381942
CRK	ENST00000574295.1	c.399+3885A>G		intron_variant		5		ENSP00000459505
CRK	ENST00000572145.1	n.576+3677A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21872 AN: 151964 Hom.: 2041 Cov.: 31

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.0833

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.0525

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0827

Gnomad OTH AF: 0.138

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

GnomAD4 genome AF: 0.144 AC: 21869 AN: 152082 Hom.: 2043 Cov.: 31 AF XY: 0.144 AC XY: 10717 AN XY: 74354

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.0833

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.0513

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.0827

Gnomad4 OTH AF: 0.135

Alfa AF: 0.117 Hom.: 373

Bravo AF: 0.156

Asia WGS AF: 0.0990 AC: 347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.13
DANN	Benign	0.46

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: rs8073032; hg19: chr17-1336407; COSMIC: COSV56032315;