17-1433088-G-C

Variant names:

• chr17-1433088-G-C
• rs8064892
• NM_016823.4:c.777+3532C>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+3532C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,054 control chromosomes in the GnomAD database, including 2,261 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 0.15 (2261 hom., cov: 31)
• Consequence: CRK NM_016823.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.121
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRK	NM_016823.4	c.777+3532C>G		intron_variant	Intron 2 of 2	ENST00000300574.3	NP_058431.2
CRK	NM_005206.5	c.607+3702C>G		intron_variant	Intron 2 of 2		NP_005197.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRK	ENST00000300574.3	c.777+3532C>G		intron_variant	Intron 2 of 2	1	NM_016823.4	ENSP00000300574.2
CRK	ENST00000398970.5	c.607+3702C>G		intron_variant	Intron 2 of 2	1		ENSP00000381942.5
CRK	ENST00000574295.1	c.399+3910C>G		intron_variant	Intron 2 of 2	5		ENSP00000459505.1
CRK	ENST00000572145.1	n.576+3702C>G		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22639 AN: 151936 Hom.: 2258 Cov.: 31

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.0516

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.0833

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.0528

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0830

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.149 AC: 22641 AN: 152054 Hom.: 2261 Cov.: 31 AF XY: 0.149 AC XY: 11094 AN XY: 74326

African (AFR) AF: 0.277 AC: 11498 AN: 41456

American (AMR) AF: 0.175 AC: 2666 AN: 15252

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

East Asian (EAS) AF: 0.107 AC: 555 AN: 5174

South Asian (SAS) AF: 0.0516 AC: 249 AN: 4824

European-Finnish (FIN) AF: 0.131 AC: 1385 AN: 10552

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

European-Non Finnish (NFE) AF: 0.0830 AC: 5645 AN: 68014

Other (OTH) AF: 0.136 AC: 287 AN: 2108

Alfa AF: 0.0246 Hom.: 11

Bravo AF: 0.161

Asia WGS AF: 0.102 AC: 357 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.56
PhyloP100		-0.12
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: rs8064892; hg19: chr17-1336382; COSMIC: COSV56032306;