chr8-55991051-G-A

Variant names:

• chr8-55991051-G-A
• rs9650314
• NM_002350.4:c.1051-7295G>A

Variant summary

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

The NM_002350.4(LYN):​c.1051-7295G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,128 control chromosomes in the GnomAD database, including 2,201 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 0.15 (2201 hom., cov: 32)
• Consequence: LYN NM_002350.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19
• Publications: 6 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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.207 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.1051-7295G>A		intron	N/A	NP_002341.1
	LYN	NM_001111097.3		c.988-7295G>A		intron	N/A	NP_001104567.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYN	ENST00000519728.6	TSL:1 MANE Select	c.1051-7295G>A		intron	N/A	ENSP00000428924.1
	LYN	ENST00000520220.6	TSL:1	c.988-7295G>A		intron	N/A	ENSP00000428424.1
	LYN	ENST00000420292.1	TSL:3	n.459-7295G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22297 AN: 152010 Hom.: 2200 Cov.: 32

Gnomad AFR AF: 0.0365

Gnomad AMI AF: 0.375

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0992

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.147 AC: 22296 AN: 152128 Hom.: 2201 Cov.: 32 AF XY: 0.143 AC XY: 10623 AN XY: 74358

African (AFR) AF: 0.0365 AC: 1516 AN: 41506

American (AMR) AF: 0.166 AC: 2529 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1017 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5184

South Asian (SAS) AF: 0.0995 AC: 480 AN: 4826

European-Finnish (FIN) AF: 0.163 AC: 1728 AN: 10574

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14236 AN: 67978

Other (OTH) AF: 0.177 AC: 374 AN: 2114

Alfa AF: 0.199 Hom.: 4024

Bravo AF: 0.143

Asia WGS AF: 0.0510 AC: 179 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	6.8
DANN	Benign	0.47
PhyloP100		1.2
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: rs9650314; hg19: chr8-56903610;