8-55934611-A-G

Variant names:

• chr8-55934611-A-G
• rs13249338
• NM_002350.4:c.-5-7244A>G

Variant summary

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

The NM_002350.4(LYN):​c.-5-7244A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 152,102 control chromosomes in the GnomAD database, including 23,517 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 0.54 (23517 hom., cov: 32)
• Consequence: LYN NM_002350.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.641 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.-5-7244A>G		intron	N/A	NP_002341.1	P07948-1
	LYN	NM_001111097.3		c.-5-7244A>G		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.-5-7244A>G		intron	N/A	ENSP00000428924.1	P07948-1
	LYN	ENST00000520220.6	TSL:1	c.-5-7244A>G		intron	N/A	ENSP00000428424.1	P07948-2
	LYN	ENST00000862998.1		c.-5-7244A>G		intron	N/A	ENSP00000533057.1

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82807 AN: 151984 Hom.: 23512 Cov.: 32

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.709

Gnomad EAS AF: 0.660

Gnomad SAS AF: 0.597

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.577

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

GnomAD4 genome AF: 0.545 AC: 82844 AN: 152102 Hom.: 23517 Cov.: 32 AF XY: 0.544 AC XY: 40464 AN XY: 74374

African (AFR) AF: 0.391 AC: 16231 AN: 41492

American (AMR) AF: 0.516 AC: 7884 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.709 AC: 2460 AN: 3468

East Asian (EAS) AF: 0.659 AC: 3399 AN: 5154

South Asian (SAS) AF: 0.597 AC: 2884 AN: 4828

European-Finnish (FIN) AF: 0.601 AC: 6368 AN: 10598

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.611 AC: 41533 AN: 67956

Other (OTH) AF: 0.582 AC: 1226 AN: 2108

Alfa AF: 0.587 Hom.: 23789

Bravo AF: 0.532

Asia WGS AF: 0.619 AC: 2151 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.53
DANN	Benign	0.80
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: rs13249338; hg19: chr8-56847170;