8-55992293-T-C

Variant names:

• chr8-55992293-T-C
• rs2719252
• NM_002350.4:c.1051-6053T>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.1051-6053T>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 152,032 control chromosomes in the GnomAD database, including 5,788 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 (5788 hom., cov: 32)
• Consequence: LYN NM_002350.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYN	NM_002350.4	c.1051-6053T>C		intron_variant	Intron 10 of 12	ENST00000519728.6	NP_002341.1
LYN	NM_001111097.3	c.988-6053T>C		intron_variant	Intron 10 of 12		NP_001104567.1
LYN	XM_011517529.4	c.784-6053T>C		intron_variant	Intron 9 of 11		XP_011515831.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LYN	ENST00000519728.6	c.1051-6053T>C		intron_variant	Intron 10 of 12	1	NM_002350.4	ENSP00000428924.1
LYN	ENST00000520220.6	c.988-6053T>C		intron_variant	Intron 10 of 12	1		ENSP00000428424.1
LYN	ENST00000420292.1	n.459-6053T>C		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40216 AN: 151914 Hom.: 5782 Cov.: 32

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.397

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.0266

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.265 AC: 40250 AN: 152032 Hom.: 5788 Cov.: 32 AF XY: 0.258 AC XY: 19166 AN XY: 74346

African (AFR) AF: 0.354 AC: 14649 AN: 41430

American (AMR) AF: 0.242 AC: 3702 AN: 15290

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

East Asian (EAS) AF: 0.0266 AC: 138 AN: 5182

South Asian (SAS) AF: 0.142 AC: 684 AN: 4822

European-Finnish (FIN) AF: 0.183 AC: 1935 AN: 10570

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

European-Non Finnish (NFE) AF: 0.249 AC: 16906 AN: 67952

Other (OTH) AF: 0.281 AC: 593 AN: 2110

Alfa AF: 0.117 Hom.: 189

Bravo AF: 0.275

Asia WGS AF: 0.109 AC: 381 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.6
DANN	Benign	0.65
PhyloP100		-0.014
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: rs2719252; hg19: chr8-56904852;