rs1912818

Variant names:

• chr8-55991762-T-G
• rs1912818
• NM_002350.4:c.1051-6584T>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.1051-6584T>G 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 152,098 control chromosomes in the GnomAD database, including 5,796 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 (5796 hom., cov: 32)
• Consequence: LYN NM_002350.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.615
• Publications: 5 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 = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYN	NM_002350.4	c.1051-6584T>G		intron_variant	Intron 10 of 12	ENST00000519728.6	NP_002341.1
LYN	NM_001111097.3	c.988-6584T>G		intron_variant	Intron 10 of 12		NP_001104567.1
LYN	XM_011517529.4	c.784-6584T>G		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.1051-6584T>G		intron_variant	Intron 10 of 12	1	NM_002350.4	ENSP00000428924.1
LYN	ENST00000520220.6	c.988-6584T>G		intron_variant	Intron 10 of 12	1		ENSP00000428424.1
LYN	ENST00000420292.1	n.459-6584T>G		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40244 AN: 151980 Hom.: 5790 Cov.: 32

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.398

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.0266

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.283

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

GnomAD4 genome AF: 0.265 AC: 40278 AN: 152098 Hom.: 5796 Cov.: 32 AF XY: 0.258 AC XY: 19166 AN XY: 74366

African (AFR) AF: 0.354 AC: 14668 AN: 41460

American (AMR) AF: 0.242 AC: 3698 AN: 15280

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

East Asian (EAS) AF: 0.0267 AC: 138 AN: 5178

South Asian (SAS) AF: 0.142 AC: 683 AN: 4824

European-Finnish (FIN) AF: 0.183 AC: 1938 AN: 10578

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

European-Non Finnish (NFE) AF: 0.249 AC: 16919 AN: 67994

Other (OTH) AF: 0.280 AC: 590 AN: 2108

Alfa AF: 0.254 Hom.: 680

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	-0.90
CADD	Benign	1.1
DANN	Benign	0.47
PhyloP100		-0.61
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: rs1912818; hg19: chr8-56904321;