rs868541

Variant names:

• chr8-55964201-C-T
• rs868541
• NM_002350.4:c.791-2514C>T

Variant summary

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

The NM_002350.4(LYN):​c.791-2514C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 151,794 control chromosomes in the GnomAD database, including 17,495 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 0.47 (17495 hom., cov: 31)
• Consequence: LYN NM_002350.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.618
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYN	NM_002350.4	c.791-2514C>T		intron_variant	Intron 8 of 12	ENST00000519728.6	NP_002341.1
LYN	NM_001111097.3	c.728-2514C>T		intron_variant	Intron 8 of 12		NP_001104567.1
LYN	XM_011517529.4	c.524-2514C>T		intron_variant	Intron 7 of 11		XP_011515831.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LYN	ENST00000519728.6	c.791-2514C>T		intron_variant	Intron 8 of 12	1	NM_002350.4	ENSP00000428924.1
LYN	ENST00000520220.6	c.728-2514C>T		intron_variant	Intron 8 of 12	1		ENSP00000428424.1
LYN	ENST00000420292.1	n.199-2514C>T		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71196 AN: 151676 Hom.: 17470 Cov.: 31

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.683

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.510

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

GnomAD4 genome AF: 0.469 AC: 71265 AN: 151794 Hom.: 17495 Cov.: 31 AF XY: 0.459 AC XY: 34073 AN XY: 74178

African (AFR) AF: 0.586 AC: 24263 AN: 41390

American (AMR) AF: 0.395 AC: 6019 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 1682 AN: 3470

East Asian (EAS) AF: 0.267 AC: 1385 AN: 5180

South Asian (SAS) AF: 0.292 AC: 1404 AN: 4814

European-Finnish (FIN) AF: 0.346 AC: 3628 AN: 10472

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.457 AC: 31023 AN: 67900

Other (OTH) AF: 0.510 AC: 1076 AN: 2110

Alfa AF: 0.459 Hom.: 2611

Bravo AF: 0.477

Asia WGS AF: 0.296 AC: 1031 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.4
DANN	Benign	0.71
PhyloP100		0.62
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: rs868541; hg19: chr8-56876760;