rs7208768

Positions:

• chr17-1449407-G-A
• chr17-1449407-G-T

Variant summary

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

The NM_016823.4(CRK):​c.241+6470C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 151,972 control chromosomes in the GnomAD database, including 23,935 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 0.55 (23935 hom., 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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRK	NM_016823.4	c.241+6470C>T		intron_variant		ENST00000300574.3
CRK	NM_005206.5	c.241+6470C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRK	ENST00000300574.3	c.241+6470C>T		intron_variant		1	NM_016823.4	P1
CRK	ENST00000398970.5	c.241+6470C>T		intron_variant		1
CRK	ENST00000574295.1	c.241+6470C>T		intron_variant		5
CRK	ENST00000572145.1	n.211-12252C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84238 AN: 151854 Hom.: 23907 Cov.: 32

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.642

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.584

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

GnomAD4 genome AF: 0.555 AC: 84315 AN: 151972 Hom.: 23935 Cov.: 32 AF XY: 0.550 AC XY: 40828 AN XY: 74264

Gnomad4 AFR AF: 0.443

Gnomad4 AMR AF: 0.558

Gnomad4 ASJ AF: 0.577

Gnomad4 EAS AF: 0.422

Gnomad4 SAS AF: 0.644

Gnomad4 FIN AF: 0.516

Gnomad4 NFE AF: 0.629

Gnomad4 OTH AF: 0.585

Alfa AF: 0.607 Hom.: 44339

Bravo AF: 0.544

Asia WGS AF: 0.531 AC: 1849 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	1.4
DANN	Benign	0.23

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;