Genetic Variant LYN:c.974-93A>G (chr8-55969624-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_002350.4(LYN):c.974-93A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 930,604 control chromosomes in the GnomAD database, including 85,906 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 0.43 ( 14595 hom., cov: 33)

Exomes 𝑓: 0.42 ( 71311 hom. )

Consequence

LYN
NM_002350.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.36

Publications

7 publications found

Variant links:

Genes affected

LYN (HGNC:6735): (LYN proto-oncogene, Src family tyrosine kinase) This gene encodes a tyrosine protein kinase, which maybe involved in the regulation of mast cell degranulation, and erythroid differentiation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2011]

LYN Gene-Disease associations (from GenCC):

autoinflammatory disease, systemic, with vasculitis
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

LYN links:

Genome browser will be placed here

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=-0.85).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002350.4. 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
	LYN	NM_002350.4	MANE Select	c.974-93A>G		intron	N/A	NP_002341.1
	LYN	NM_001111097.3		c.911-93A>G		intron	N/A	NP_001104567.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
LYN	ENST00000519728.6	TSL:1 MANE Select	c.974-93A>G	intron	N/A	ENSP00000428924.1
LYN	ENST00000520220.6	TSL:1	c.911-93A>G	intron	N/A	ENSP00000428424.1
LYN	ENST00000420292.1	TSL:3	n.382-93A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.432

AC:

65618

AN:

151988

Hom.:

14591

Cov.:

show subpopulations

Gnomad AFR

AF:

0.457

Gnomad AMI

AF:

0.685

Gnomad AMR

AF:

0.384

Gnomad ASJ

AF:

0.485

Gnomad EAS

AF:

0.248

Gnomad SAS

AF:

0.291

Gnomad FIN

AF:

0.345

Gnomad MID

AF:

0.547

Gnomad NFE

AF:

0.456

Gnomad OTH

AF:

0.484

GnomAD4 exome

AF:

0.420

AC:

326926

AN:

778498

Hom.:

71311

AF XY:

0.418

AC XY:

172118

AN XY:

411524

show subpopulations

African (AFR)

AF:

0.456

AC:

9318

AN:

20414

American (AMR)

AF:

0.280

AC:

11985

AN:

42768

Ashkenazi Jewish (ASJ)

AF:

0.513

AC:

11094

AN:

21606

East Asian (EAS)

AF:

0.261

AC:

9483

AN:

36308

South Asian (SAS)

AF:

0.303

AC:

21723

AN:

71712

European-Finnish (FIN)

AF:

0.352

AC:

17604

AN:

49956

Middle Eastern (MID)

AF:

0.542

AC:

2300

AN:

4242

European-Non Finnish (NFE)

AF:

0.459

AC:

226895

AN:

493824

Other (OTH)

AF:

0.439

AC:

16524

AN:

37668

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

9199

18399

27598

36798

45997

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3694

7388

11082

14776

18470

<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:

0.432

AC:

65657

AN:

152106

Hom.:

14595

Cov.:

AF XY:

0.422

AC XY:

31370

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.457

AC:

18975

AN:

41492

American (AMR)

AF:

0.383

AC:

5852

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.485

AC:

1679

AN:

3464

East Asian (EAS)

AF:

0.247

AC:

1284

AN:

5188

South Asian (SAS)

AF:

0.291

AC:

1405

AN:

4830

European-Finnish (FIN)

AF:

0.345

AC:

3642

AN:

10564

Middle Eastern (MID)

AF:

0.541

AC:

159

AN:

294

European-Non Finnish (NFE)

AF:

0.456

AC:

31013

AN:

67966

Other (OTH)

AF:

0.485

AC:

1025

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1940

3880

5819

7759

9699

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

604

1208

1812

2416

3020

<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:

0.427

Hom.:

8443

Bravo

AF:

0.437

Asia WGS

AF:

0.284

AC:

989

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.24

(source)

DANN

Benign

0.48

PhyloP100

-1.4

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over