rs7208768

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 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 (SAS) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRK	NM_016823.4	c.241+6470C>T		intron_variant	Intron 1 of 2	ENST00000300574.3	NP_058431.2
CRK	NM_005206.5	c.241+6470C>T		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>T		intron_variant	Intron 1 of 2	1	NM_016823.4	ENSP00000300574.2
CRK	ENST00000398970.5	c.241+6470C>T		intron_variant	Intron 1 of 2	1		ENSP00000381942.5
CRK	ENST00000574295.1	c.241+6470C>T		intron_variant	Intron 1 of 2	5		ENSP00000459505.1
CRK	ENST00000572145.1	n.211-12252C>T		intron_variant	Intron 1 of 2	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

African (AFR) AF: 0.443 AC: 18375 AN: 41434

American (AMR) AF: 0.558 AC: 8513 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.577 AC: 2004 AN: 3472

East Asian (EAS) AF: 0.422 AC: 2183 AN: 5176

South Asian (SAS) AF: 0.644 AC: 3103 AN: 4820

European-Finnish (FIN) AF: 0.516 AC: 5436 AN: 10528

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.629 AC: 42730 AN: 67986

Other (OTH) AF: 0.585 AC: 1232 AN: 2106

Alfa AF: 0.594 Hom.: 67502

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
PhyloP100		-0.24
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: rs7208768; hg19: chr17-1352701;