Genetic Variant FYN:c.1405+36T>C (chr6-111674463-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.1405+36T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,572,492 control chromosomes in the GnomAD database, including 18,334 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 0.19 ( 3528 hom., cov: 32)

Exomes 𝑓: 0.13 ( 14806 hom. )

Consequence

FYN
NM_002037.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.953

Publications

17 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=-0.75).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FYN	NM_002037.5 link	c.1405+36T>C		intron_variant	Intron 13 of 13	ENST00000354650.7	NP_002028.1	P06241-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FYN	ENST00000354650.7 link	c.1405+36T>C		intron_variant	Intron 13 of 13	1	NM_002037.5	ENSP00000346671.3		P06241-1

Frequencies

GnomAD3 genomes

AF:

0.189

AC:

28696

AN:

152006

Hom.:

3522

Cov.:

show subpopulations

Gnomad AFR

AF:

0.340

Gnomad AMI

AF:

0.207

Gnomad AMR

AF:

0.128

Gnomad ASJ

AF:

0.108

Gnomad EAS

AF:

0.298

Gnomad SAS

AF:

0.0576

Gnomad FIN

AF:

0.117

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.128

Gnomad OTH

AF:

0.154

GnomAD2 exomes

AF:

0.142

AC:

33050

AN:

232120

AF XY:

0.135

show subpopulations

Gnomad AFR exome

AF:

0.349

Gnomad AMR exome

AF:

0.115

Gnomad ASJ exome

AF:

0.101

Gnomad EAS exome

AF:

0.293

Gnomad FIN exome

AF:

0.113

Gnomad NFE exome

AF:

0.130

Gnomad OTH exome

AF:

0.117

GnomAD4 exome

AF:

0.133

AC:

189561

AN:

1420368

Hom.:

14806

Cov.:

AF XY:

0.131

AC XY:

91877

AN XY:

702926

show subpopulations

African (AFR)

AF:

0.353

AC:

11253

AN:

31872

American (AMR)

AF:

0.113

AC:

4521

AN:

39866

Ashkenazi Jewish (ASJ)

AF:

0.0997

AC:

2457

AN:

24654

East Asian (EAS)

AF:

0.326

AC:

12541

AN:

38428

South Asian (SAS)

AF:

0.0495

AC:

4035

AN:

81586

European-Finnish (FIN)

AF:

0.112

AC:

5898

AN:

52624

Middle Eastern (MID)

AF:

0.0703

AC:

391

AN:

5564

European-Non Finnish (NFE)

AF:

0.129

AC:

140493

AN:

1087486

Other (OTH)

AF:

0.137

AC:

7972

AN:

58288

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

7253

14506

21758

29011

36264

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.189

AC:

28725

AN:

152124

Hom.:

3528

Cov.:

AF XY:

0.187

AC XY:

13909

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.340

AC:

14091

AN:

41440

American (AMR)

AF:

0.128

AC:

1954

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.108

AC:

376

AN:

3468

East Asian (EAS)

AF:

0.298

AC:

1544

AN:

5176

South Asian (SAS)

AF:

0.0576

AC:

278

AN:

4824

European-Finnish (FIN)

AF:

0.117

AC:

1246

AN:

10606

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.128

AC:

8694

AN:

68004

Other (OTH)

AF:

0.153

AC:

323

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1116

2232

3347

4463

5579

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.158

Hom.:

4429

Bravo

AF:

0.198

Asia WGS

AF:

0.180

AC:

626

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

5.0

(source)

DANN

Benign

0.86

PhyloP100

0.95

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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6-111674463-A-G

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