Genetic Variant NM_016823.4:c.*1510T>C (chr17-1422003-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_016823.4(CRK):c.*1510T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 151,938 control chromosomes in the GnomAD database, including 2,068 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 ( 2068 hom., cov: 31)

Failed GnomAD Quality Control

Consequence

CRK
NM_016823.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.249

Publications

16 publications found

Variant links:

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]

CRK links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.258 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.*1510T>C		3_prime_UTR	Exon 3 of 3	NP_058431.2
	CRK	NM_005206.5		c.*1640T>C		3_prime_UTR	Exon 3 of 3	NP_005197.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CRK	ENST00000300574.3	TSL:1 MANE Select	c.*1510T>C	3_prime_UTR	Exon 3 of 3	ENSP00000300574.2
CRK	ENST00000398970.5	TSL:1	c.*1640T>C	3_prime_UTR	Exon 3 of 3	ENSP00000381942.5
CRK	ENST00000574295.1	TSL:5	c.*910T>C	downstream_gene	N/A	ENSP00000459505.1

Frequencies

GnomAD3 genomes

AF:

0.144

AC:

21927

AN:

151820

Hom.:

2065

Cov.:

show subpopulations

Gnomad AFR

AF:

0.263

Gnomad AMI

AF:

0.0515

Gnomad AMR

AF:

0.173

Gnomad ASJ

AF:

0.0824

Gnomad EAS

AF:

0.107

Gnomad SAS

AF:

0.0527

Gnomad FIN

AF:

0.131

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0828

Gnomad OTH

AF:

0.139

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.144

AC:

21928

AN:

151938

Hom.:

2068

Cov.:

AF XY:

0.145

AC XY:

10769

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.262

AC:

10843

AN:

41382

American (AMR)

AF:

0.173

AC:

2631

AN:

15222

Ashkenazi Jewish (ASJ)

AF:

0.0824

AC:

286

AN:

3470

East Asian (EAS)

AF:

0.107

AC:

555

AN:

5176

South Asian (SAS)

AF:

0.0513

AC:

247

AN:

4812

European-Finnish (FIN)

AF:

0.131

AC:

1384

AN:

10572

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0828

AC:

5627

AN:

67986

Other (OTH)

AF:

0.136

AC:

288

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

891

1783

2674

3566

4457

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

228

456

684

912

1140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0992

Hom.:

3734

Bravo

AF:

0.156

Asia WGS

AF:

0.100

AC:

351

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.5

(source)

DANN

Benign

0.76

PhyloP100

0.25

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over