rs2668021

Variant names:

• chr8-55960988-T-C
• rs2668021
• NM_002350.4:c.791-5727T>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.791-5727T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,056 control chromosomes in the GnomAD database, including 6,114 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 0.27 (6114 hom., cov: 32)
• Consequence: LYN NM_002350.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.166
• Publications: 11 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.371 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.791-5727T>C		intron	N/A	NP_002341.1
	LYN	NM_001111097.3		c.728-5727T>C		intron	N/A	NP_001104567.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYN	ENST00000519728.6	TSL:1 MANE Select	c.791-5727T>C		intron	N/A	ENSP00000428924.1
	LYN	ENST00000520220.6	TSL:1	c.728-5727T>C		intron	N/A	ENSP00000428424.1
	LYN	ENST00000862998.1		c.791-5700T>C		intron	N/A	ENSP00000533057.1

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40775 AN: 151938 Hom.: 6102 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.00615

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.195

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.268 AC: 40814 AN: 152056 Hom.: 6114 Cov.: 32 AF XY: 0.261 AC XY: 19432 AN XY: 74336

African (AFR) AF: 0.376 AC: 15596 AN: 41456

American (AMR) AF: 0.236 AC: 3611 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 934 AN: 3464

East Asian (EAS) AF: 0.00617 AC: 32 AN: 5188

South Asian (SAS) AF: 0.131 AC: 632 AN: 4814

European-Finnish (FIN) AF: 0.195 AC: 2060 AN: 10584

Middle Eastern (MID) AF: 0.325 AC: 95 AN: 292

European-Non Finnish (NFE) AF: 0.249 AC: 16911 AN: 67956

Other (OTH) AF: 0.269 AC: 568 AN: 2110

Alfa AF: 0.261 Hom.: 8895

Bravo AF: 0.277

Asia WGS AF: 0.0940 AC: 328 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.13
DANN	Benign	0.34
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2668021; hg19: chr8-56873547;