rs8073032

Variant names:

• chr17-1433113-T-C
• rs8073032
• NM_016823.4:c.777+3507A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016823.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRK	NM_016823.4	MANE Select	c.777+3507A>G		intron	N/A	NP_058431.2
	CRK	NM_005206.5		c.607+3677A>G		intron	N/A	NP_005197.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRK	ENST00000300574.3	TSL:1 MANE Select	c.777+3507A>G		intron	N/A	ENSP00000300574.2
	CRK	ENST00000398970.5	TSL:1	c.607+3677A>G		intron	N/A	ENSP00000381942.5
	CRK	ENST00000574295.1	TSL:5	c.399+3885A>G		intron	N/A	ENSP00000459505.1

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

African (AFR) AF: 0.260 AC: 10787 AN: 41452

American (AMR) AF: 0.172 AC: 2630 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0833 AC: 289 AN: 3470

East Asian (EAS) AF: 0.107 AC: 553 AN: 5168

South Asian (SAS) AF: 0.0513 AC: 248 AN: 4832

European-Finnish (FIN) AF: 0.131 AC: 1383 AN: 10578

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0827 AC: 5626 AN: 68008

Other (OTH) AF: 0.135 AC: 286 AN: 2112

Alfa AF: 0.119 Hom.: 390

Bravo AF: 0.156

Asia WGS AF: 0.0990 AC: 347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.13
DANN	Benign	0.46
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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