Genetic Variant LYN:c.1050+119A>G (chr8-55969912-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.1050+119A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 854,800 control chromosomes in the GnomAD database, including 77,681 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 ( 14606 hom., cov: 33)

Exomes 𝑓: 0.41 ( 63075 hom. )

Consequence

LYN
NM_002350.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0900

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=-0.79).

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.1050+119A>G		intron	N/A	NP_002341.1
	LYN	NM_001111097.3		c.987+119A>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.1050+119A>G	intron	N/A	ENSP00000428924.1
LYN	ENST00000520220.6	TSL:1	c.987+119A>G	intron	N/A	ENSP00000428424.1
LYN	ENST00000420292.1	TSL:3	n.458+119A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.432

AC:

65618

AN:

152024

Hom.:

14602

Cov.:

show subpopulations

Gnomad AFR

AF:

0.457

Gnomad AMI

AF:

0.685

Gnomad AMR

AF:

0.383

Gnomad ASJ

AF:

0.485

Gnomad EAS

AF:

0.248

Gnomad SAS

AF:

0.289

Gnomad FIN

AF:

0.345

Gnomad MID

AF:

0.547

Gnomad NFE

AF:

0.456

Gnomad OTH

AF:

0.483

GnomAD4 exome

AF:

0.414

AC:

290765

AN:

702658

Hom.:

63075

AF XY:

0.412

AC XY:

153712

AN XY:

372846

show subpopulations

African (AFR)

AF:

0.453

AC:

8544

AN:

18874

American (AMR)

AF:

0.286

AC:

10757

AN:

37590

Ashkenazi Jewish (ASJ)

AF:

0.514

AC:

10312

AN:

20068

East Asian (EAS)

AF:

0.261

AC:

9268

AN:

35576

South Asian (SAS)

AF:

0.303

AC:

20591

AN:

67852

European-Finnish (FIN)

AF:

0.355

AC:

15181

AN:

42724

Middle Eastern (MID)

AF:

0.541

AC:

2263

AN:

4180

European-Non Finnish (NFE)

AF:

0.451

AC:

198606

AN:

440794

Other (OTH)

AF:

0.436

AC:

15243

AN:

35000

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

8171

16342

24512

32683

40854

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2828

5656

8484

11312

14140

<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:

65658

AN:

152142

Hom.:

14606

Cov.:

AF XY:

0.422

AC XY:

31370

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.457

AC:

18969

AN:

41494

American (AMR)

AF:

0.383

AC:

5852

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.485

AC:

1682

AN:

3470

East Asian (EAS)

AF:

0.247

AC:

1280

AN:

5178

South Asian (SAS)

AF:

0.289

AC:

1396

AN:

4824

European-Finnish (FIN)

AF:

0.345

AC:

3647

AN:

10570

Middle Eastern (MID)

AF:

0.541

AC:

159

AN:

294

European-Non Finnish (NFE)

AF:

0.456

AC:

31030

AN:

68004

Other (OTH)

AF:

0.484

AC:

1020

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1911

3821

5732

7642

9553

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:

0.453

Hom.:

20328

Bravo

AF:

0.437

Asia WGS

AF:

0.283

AC:

987

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.1

(source)

DANN

Benign

0.55

PhyloP100

0.090

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over