rs2719243

Variant names:

• chr8-55994417-T-C
• rs2719243
• NM_002350.4:c.1051-3929T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002350.4(LYN):​c.1051-3929T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,158 control chromosomes in the GnomAD database, including 5,803 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 0.26 (5803 hom., cov: 32)
• Consequence: LYN NM_002350.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.514
• Publications: 4 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.349 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYN	NM_002350.4	MANE Select	c.1051-3929T>C		intron	N/A	NP_002341.1	P07948-1
	LYN	NM_001111097.3		c.988-3929T>C		intron	N/A	NP_001104567.1	P07948-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYN	ENST00000519728.6	TSL:1 MANE Select	c.1051-3929T>C		intron	N/A	ENSP00000428924.1	P07948-1
	LYN	ENST00000520220.6	TSL:1	c.988-3929T>C		intron	N/A	ENSP00000428424.1	P07948-2
	LYN	ENST00000862998.1		c.1078-3929T>C		intron	N/A	ENSP00000533057.1

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40269 AN: 152040 Hom.: 5797 Cov.: 32

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.0265

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.285

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.265 AC: 40303 AN: 152158 Hom.: 5803 Cov.: 32 AF XY: 0.258 AC XY: 19190 AN XY: 74398

African (AFR) AF: 0.354 AC: 14684 AN: 41484

American (AMR) AF: 0.242 AC: 3707 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 1186 AN: 3472

East Asian (EAS) AF: 0.0266 AC: 138 AN: 5186

South Asian (SAS) AF: 0.142 AC: 686 AN: 4828

European-Finnish (FIN) AF: 0.183 AC: 1933 AN: 10582

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16913 AN: 67992

Other (OTH) AF: 0.282 AC: 597 AN: 2114

Alfa AF: 0.259 Hom.: 733

Bravo AF: 0.275

Asia WGS AF: 0.109 AC: 381 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.7
DANN	Benign	0.78
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2719243; hg19: chr8-56906976; COSMIC: COSV107515502;