rs10095917

Variant names:

• chr8-55917701-C-T
• rs10095917
• NM_002350.4:c.-5-24154C>T

Variant summary

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

The NM_002350.4(LYN):​c.-5-24154C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,108 control chromosomes in the GnomAD database, including 5,318 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 0.25 (5318 hom., cov: 32)
• Consequence: LYN NM_002350.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0500
• Publications: 8 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.361 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.-5-24154C>T		intron	N/A	NP_002341.1	P07948-1
	LYN	NM_001111097.3		c.-5-24154C>T		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.-5-24154C>T		intron	N/A	ENSP00000428924.1	P07948-1
	LYN	ENST00000520220.6	TSL:1	c.-5-24154C>T		intron	N/A	ENSP00000428424.1	P07948-2
	LYN	ENST00000862998.1		c.-5-24154C>T		intron	N/A	ENSP00000533057.1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37934 AN: 151990 Hom.: 5305 Cov.: 32

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.0245

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.265

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

GnomAD4 genome AF: 0.250 AC: 37983 AN: 152108 Hom.: 5318 Cov.: 32 AF XY: 0.244 AC XY: 18133 AN XY: 74364

African (AFR) AF: 0.366 AC: 15162 AN: 41468

American (AMR) AF: 0.216 AC: 3293 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1006 AN: 3472

East Asian (EAS) AF: 0.0246 AC: 127 AN: 5172

South Asian (SAS) AF: 0.159 AC: 766 AN: 4830

European-Finnish (FIN) AF: 0.149 AC: 1577 AN: 10592

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.221 AC: 15050 AN: 67986

Other (OTH) AF: 0.262 AC: 554 AN: 2114

Alfa AF: 0.232 Hom.: 2690

Bravo AF: 0.260

Asia WGS AF: 0.114 AC: 397 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.14
PhyloP100		0.050
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: rs10095917; hg19: chr8-56830260;