rs2719232

Variant names:

• chr8-55973625-G-A
• rs2719232
• NM_002350.4:c.1050+3832G>A

Variant summary

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

The NM_002350.4(LYN):​c.1050+3832G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 152,070 control chromosomes in the GnomAD database, including 17,673 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 (17673 hom., cov: 33)
• Consequence: LYN NM_002350.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.339
• 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=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYN	NM_002350.4	c.1050+3832G>A		intron_variant	Intron 10 of 12	ENST00000519728.6	NP_002341.1
LYN	NM_001111097.3	c.987+3832G>A		intron_variant	Intron 10 of 12		NP_001104567.1
LYN	XM_011517529.4	c.783+3832G>A		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.1050+3832G>A		intron_variant	Intron 10 of 12	1	NM_002350.4	ENSP00000428924.1
LYN	ENST00000520220.6	c.987+3832G>A		intron_variant	Intron 10 of 12	1		ENSP00000428424.1
LYN	ENST00000420292.1	n.458+3832G>A		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71450 AN: 151952 Hom.: 17645 Cov.: 33

Gnomad AFR AF: 0.594

Gnomad AMI AF: 0.683

Gnomad AMR AF: 0.395

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.510

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

GnomAD4 genome AF: 0.470 AC: 71522 AN: 152070 Hom.: 17673 Cov.: 33 AF XY: 0.460 AC XY: 34173 AN XY: 74320

African (AFR) AF: 0.594 AC: 24637 AN: 41486

American (AMR) AF: 0.395 AC: 6031 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.485 AC: 1683 AN: 3470

East Asian (EAS) AF: 0.247 AC: 1279 AN: 5174

South Asian (SAS) AF: 0.290 AC: 1400 AN: 4826

European-Finnish (FIN) AF: 0.344 AC: 3632 AN: 10544

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

European-Non Finnish (NFE) AF: 0.456 AC: 30998 AN: 67974

Other (OTH) AF: 0.510 AC: 1077 AN: 2110

Alfa AF: 0.469 Hom.: 4133

Bravo AF: 0.479

Asia WGS AF: 0.293 AC: 1022 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	5.6
DANN	Benign	0.69
PhyloP100		-0.34
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: rs2719232; hg19: chr8-56886184;