Genetic Variant FYN:c.-12+25841T>C (chr6-111754725-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_002037.5(FYN):c.-12+25841T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.576 in 151,976 control chromosomes in the GnomAD database, including 26,744 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 0.58 ( 26744 hom., cov: 30)

Exomes 𝑓: 0.50 ( 0 hom. )

Consequence

FYN
NM_002037.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.22

Publications

8 publications found

Variant links:

Genes affected

FYN (HGNC:4037): (FYN proto-oncogene, Src family tyrosine kinase) This gene is a member of the protein-tyrosine kinase oncogene family. It encodes a membrane-associated tyrosine kinase that has been implicated in the control of cell growth. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist. [provided by RefSeq, Jul 2008]

FYN 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=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002037.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
FYN	NM_002037.5	MANE Select	c.-12+25841T>C	intron	N/A	NP_002028.1
FYN	NM_001370529.1		c.-12+5120T>C	intron	N/A	NP_001357458.1
FYN	NM_153047.4		c.-12+25841T>C	intron	N/A	NP_694592.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
FYN	ENST00000354650.7	TSL:1 MANE Select	c.-12+25841T>C	intron	N/A	ENSP00000346671.3
FYN	ENST00000229471.8	TSL:1	c.-12+4315T>C	intron	N/A	ENSP00000229471.4
FYN	ENST00000368667.6	TSL:5	c.-12+25841T>C	intron	N/A	ENSP00000357656.2

Frequencies

GnomAD3 genomes

AF:

0.576

AC:

87415

AN:

151852

Hom.:

26707

Cov.:

show subpopulations

Gnomad AFR

AF:

0.755

Gnomad AMI

AF:

0.364

Gnomad AMR

AF:

0.625

Gnomad ASJ

AF:

0.501

Gnomad EAS

AF:

0.862

Gnomad SAS

AF:

0.614

Gnomad FIN

AF:

0.435

Gnomad MID

AF:

0.563

Gnomad NFE

AF:

0.459

Gnomad OTH

AF:

0.612

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

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)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.576

AC:

87511

AN:

151970

Hom.:

26744

Cov.:

AF XY:

0.580

AC XY:

43068

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.755

AC:

31292

AN:

41442

American (AMR)

AF:

0.626

AC:

9565

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.501

AC:

1740

AN:

3470

East Asian (EAS)

AF:

0.861

AC:

4441

AN:

5156

South Asian (SAS)

AF:

0.613

AC:

2953

AN:

4814

European-Finnish (FIN)

AF:

0.435

AC:

4586

AN:

10546

Middle Eastern (MID)

AF:

0.554

AC:

163

AN:

294

European-Non Finnish (NFE)

AF:

0.459

AC:

31157

AN:

67952

Other (OTH)

AF:

0.609

AC:

1283

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1752

3505

5257

7010

8762

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

722

1444

2166

2888

3610

<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:

0.502

Hom.:

32001

Bravo

AF:

0.602

Asia WGS

AF:

0.689

AC:

2396

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.35

(source)

DANN

Benign

0.45

PhyloP100

-1.2

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