Genetic Variant LYN:c.1050+10536G>C (chr8-55980329-G-C) – 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+10536G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,030 control chromosomes in the GnomAD database, including 8,627 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 0.31 ( 8624 hom., cov: 32)

Exomes 𝑓: 0.24 ( 3 hom. )

Consequence

LYN
NM_002350.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.206

Publications

3 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 links:

RN7SL798P (HGNC:46814): (RNA, 7SL, cytoplasmic 798, pseudogene)

RN7SL798P 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=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
LYN	NM_002350.4 link	c.1050+10536G>C	intron_variant	Intron 10 of 12	ENST00000519728.6	NP_002341.1	P07948-1Q6NUK7A8K379
RN7SL798P		n.55980329G>C	intragenic_variant
LYN	NM_001111097.3 link	c.987+10536G>C	intron_variant	Intron 10 of 12		NP_001104567.1	P07948-2Q6NUK7
LYN	XM_011517529.4 link	c.783+10536G>C	intron_variant	Intron 9 of 11		XP_011515831.2	B4DQ79

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
LYN	ENST00000519728.6 link	c.1050+10536G>C	intron_variant	Intron 10 of 12	1	NM_002350.4	ENSP00000428924.1	P07948-1
LYN	ENST00000520220.6 link	c.987+10536G>C	intron_variant	Intron 10 of 12	1		ENSP00000428424.1	P07948-2
RN7SL798P	ENST00000468562.3 link	n.212C>G	non_coding_transcript_exon_variant	Exon 1 of 1	6
LYN	ENST00000420292.1 link	n.458+10536G>C	intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.308

AC:

46809

AN:

151822

Hom.:

8594

Cov.:

show subpopulations

Gnomad AFR

AF:

0.507

Gnomad AMI

AF:

0.398

Gnomad AMR

AF:

0.254

Gnomad ASJ

AF:

0.343

Gnomad EAS

AF:

0.0283

Gnomad SAS

AF:

0.140

Gnomad FIN

AF:

0.183

Gnomad MID

AF:

0.321

Gnomad NFE

AF:

0.250

Gnomad OTH

AF:

0.317

GnomAD4 exome

AF:

0.245

AC:

AN:

Hom.:

Cov.:

AF XY:

0.212

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.189

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.537

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.309

AC:

46884

AN:

151936

Hom.:

8624

Cov.:

AF XY:

0.300

AC XY:

22277

AN XY:

74246

show subpopulations

African (AFR)

AF:

0.507

AC:

20988

AN:

41384

American (AMR)

AF:

0.253

AC:

3864

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.343

AC:

1191

AN:

3468

East Asian (EAS)

AF:

0.0284

AC:

147

AN:

5180

South Asian (SAS)

AF:

0.140

AC:

674

AN:

4820

European-Finnish (FIN)

AF:

0.183

AC:

1932

AN:

10544

Middle Eastern (MID)

AF:

0.331

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.250

AC:

16966

AN:

67966

Other (OTH)

AF:

0.314

AC:

663

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1519

3038

4556

6075

7594

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

442

884

1326

1768

2210

<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:

0.124

Hom.:

200

Bravo

AF:

0.323

Asia WGS

AF:

0.119

AC:

416

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.92

(source)

DANN

Benign

0.55

PhyloP100

-0.21

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over