rs1083

Positions:

• chr17-1422003-A-G

Variant summary

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

The NM_016823.4(CRK):​c.*1510T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 151,938 control chromosomes in the GnomAD database, including 2,068 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 (2068 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: CRK NM_016823.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.249

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRK	NM_016823.4	c.*1510T>C		3_prime_UTR_variant	3/3	ENST00000300574.3
CRK	NM_005206.5	c.*1640T>C		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRK	ENST00000300574.3	c.*1510T>C		3_prime_UTR_variant	3/3	1	NM_016823.4	P1
CRK	ENST00000398970.5	c.*1640T>C		3_prime_UTR_variant	3/3	1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21927 AN: 151820 Hom.: 2065 Cov.: 31

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.0824

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.0527

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0828

Gnomad OTH AF: 0.139

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.144 AC: 21928 AN: 151938 Hom.: 2068 Cov.: 31 AF XY: 0.145 AC XY: 10769 AN XY: 74266

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.0824

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.0513

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.0828

Gnomad4 OTH AF: 0.136

Alfa AF: 0.0899 Hom.: 1253

Bravo AF: 0.156

Asia WGS AF: 0.100 AC: 351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.5
DANN	Benign	0.76

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: rs1083; hg19: chr17-1325297; COSMIC: COSV56032249; COSMIC: COSV56032249;