Genetic Variant FRK:c.*396A>G (chr6-115942018-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002031.3(FRK):c.*396A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 171,382 control chromosomes in the GnomAD database, including 32,785 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 0.61 ( 28648 hom., cov: 32)

Exomes 𝑓: 0.64 ( 4137 hom. )

Consequence

FRK
NM_002031.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.153

Publications

13 publications found

Variant links:

Genes affected

FRK (HGNC:3955): (fyn related Src family tyrosine kinase) The protein encoded by this gene belongs to the TYR family of protein kinases. This tyrosine kinase is a nuclear protein and may function during G1 and S phase of the cell cycle and suppress growth. [provided by RefSeq, Jul 2008]

FRK links:

ENSG00000289376 (HGNC:):

ENSG00000289376 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=-0.56).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FRK	NM_002031.3 link	c.*396A>G		3_prime_UTR_variant	Exon 8 of 8	ENST00000606080.2	NP_002022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FRK	ENST00000606080.2 link	c.*396A>G		3_prime_UTR_variant	Exon 8 of 8	1	NM_002031.3	ENSP00000476145.1
ENSG00000289376	ENST00000692859.3 link	n.269-39840A>G		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.610

AC:

92616

AN:

151932

Hom.:

28631

Cov.:

show subpopulations

Gnomad AFR

AF:

0.535

Gnomad AMI

AF:

0.843

Gnomad AMR

AF:

0.562

Gnomad ASJ

AF:

0.598

Gnomad EAS

AF:

0.838

Gnomad SAS

AF:

0.742

Gnomad FIN

AF:

0.705

Gnomad MID

AF:

0.589

Gnomad NFE

AF:

0.622

Gnomad OTH

AF:

0.575

GnomAD4 exome

AF:

0.638

AC:

12336

AN:

19332

Hom.:

4137

Cov.:

AF XY:

0.647

AC XY:

6733

AN XY:

10412

show subpopulations

African (AFR)

AF:

0.410

AC:

AN:

134

American (AMR)

AF:

0.542

AC:

948

AN:

1748

Ashkenazi Jewish (ASJ)

AF:

0.575

AC:

207

AN:

360

East Asian (EAS)

AF:

0.859

AC:

507

AN:

590

South Asian (SAS)

AF:

0.727

AC:

1839

AN:

2528

European-Finnish (FIN)

AF:

0.694

AC:

937

AN:

1350

Middle Eastern (MID)

AF:

0.600

AC:

AN:

European-Non Finnish (NFE)

AF:

0.620

AC:

7230

AN:

11652

Other (OTH)

AF:

0.634

AC:

583

AN:

920

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

212

424

635

847

1059

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

136

204

272

340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.610

AC:

92679

AN:

152050

Hom.:

28648

Cov.:

AF XY:

0.617

AC XY:

45833

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.535

AC:

22194

AN:

41452

American (AMR)

AF:

0.562

AC:

8584

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.598

AC:

2076

AN:

3472

East Asian (EAS)

AF:

0.837

AC:

4331

AN:

5174

South Asian (SAS)

AF:

0.743

AC:

3589

AN:

4830

European-Finnish (FIN)

AF:

0.705

AC:

7449

AN:

10572

Middle Eastern (MID)

AF:

0.585

AC:

172

AN:

294

European-Non Finnish (NFE)

AF:

0.622

AC:

42295

AN:

67966

Other (OTH)

AF:

0.578

AC:

1220

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1820

3641

5461

7282

9102

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

774

1548

2322

3096

3870

<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:

0.602

Hom.:

34321

Bravo

AF:

0.590

Asia WGS

AF:

0.774

AC:

2689

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

8.0

(source)

DANN

Benign

0.87

PhyloP100

0.15

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over