17-1449407-G-T

Variant names:

• chr17-1449407-G-T
• rs7208768
• NM_016823.4:c.241+6470C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016823.4(CRK):​c.241+6470C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: CRK NM_016823.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.236

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRK	NM_016823.4	c.241+6470C>A		intron_variant	Intron 1 of 2	ENST00000300574.3	NP_058431.2
CRK	NM_005206.5	c.241+6470C>A		intron_variant	Intron 1 of 2		NP_005197.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRK	ENST00000300574.3	c.241+6470C>A		intron_variant	Intron 1 of 2	1	NM_016823.4	ENSP00000300574.2
CRK	ENST00000398970.5	c.241+6470C>A		intron_variant	Intron 1 of 2	1		ENSP00000381942.5
CRK	ENST00000574295.1	c.241+6470C>A		intron_variant	Intron 1 of 2	5		ENSP00000459505.1
CRK	ENST00000572145.1	n.211-12252C>A		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.58
DANN	Benign	0.22

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: rs7208768; hg19: chr17-1352701;