Genetic Variant FYN:c.-18C>A (chr6-111780572-G-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_002037.5(FYN):c.-18C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 152,492 control chromosomes in the GnomAD database, including 27,817 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 0.59 ( 27774 hom., cov: 32)

Exomes 𝑓: 0.45 ( 43 hom. )

Consequence

FYN
NM_002037.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.170

Publications

15 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.829 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FYN	NM_002037.5	MANE Select	c.-18C>A		5_prime_UTR	Exon 3 of 14	NP_002028.1	P06241-1
	FYN	NM_153047.4		c.-18C>A		5_prime_UTR	Exon 3 of 14	NP_694592.1	P06241-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FYN	ENST00000354650.7	TSL:1 MANE Select	c.-18C>A	5_prime_UTR	Exon 3 of 14	ENSP00000346671.3	P06241-1
FYN	ENST00000912320.1		c.-18C>A	5_prime_UTR	Exon 3 of 15	ENSP00000582379.1
FYN	ENST00000912326.1		c.-18C>A	5_prime_UTR	Exon 4 of 16	ENSP00000582385.1

Frequencies

GnomAD3 genomes

AF:

0.590

AC:

89579

AN:

151956

Hom.:

27734

Cov.:

show subpopulations

Gnomad AFR

AF:

0.755

Gnomad AMI

AF:

0.318

Gnomad AMR

AF:

0.652

Gnomad ASJ

AF:

0.505

Gnomad EAS

AF:

0.851

Gnomad SAS

AF:

0.627

Gnomad FIN

AF:

0.456

Gnomad MID

AF:

0.620

Gnomad NFE

AF:

0.479

Gnomad OTH

AF:

0.634

GnomAD4 exome

AF:

0.452

AC:

189

AN:

418

Hom.:

Cov.:

AF XY:

0.448

AC XY:

113

AN XY:

252

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:

0.453

AC:

185

AN:

408

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.333

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.590

AC:

89675

AN:

152074

Hom.:

27774

Cov.:

AF XY:

0.593

AC XY:

44114

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.755

AC:

31332

AN:

41500

American (AMR)

AF:

0.653

AC:

9976

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.505

AC:

1752

AN:

3470

East Asian (EAS)

AF:

0.850

AC:

4403

AN:

5180

South Asian (SAS)

AF:

0.627

AC:

3026

AN:

4826

European-Finnish (FIN)

AF:

0.456

AC:

4815

AN:

10556

Middle Eastern (MID)

AF:

0.612

AC:

180

AN:

294

European-Non Finnish (NFE)

AF:

0.479

AC:

32571

AN:

67946

Other (OTH)

AF:

0.632

AC:

1331

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1772

3545

5317

7090

8862

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

732

1464

2196

2928

3660

<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:

0.535

Hom.:

13430

Bravo

AF:

0.616

Asia WGS

AF:

0.699

AC:

2429

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.95

PhyloP100

0.17

Mutation Taster

=300/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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