rs2100245

Positions:

• chr8-55937541-A-G
• chr8-55937541-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002350.4(LYN):​c.-5-4314A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,138 control chromosomes in the GnomAD database, including 8,508 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 0.29 (8508 hom., cov: 32)
• Consequence: LYN NM_002350.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.291

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYN	NM_002350.4	c.-5-4314A>G		intron_variant		ENST00000519728.6	NP_002341.1
LYN	NM_001111097.3	c.-5-4314A>G		intron_variant			NP_001104567.1
LYN	XM_011517529.4	c.-135-8907A>G		intron_variant			XP_011515831.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYN	ENST00000519728.6	c.-5-4314A>G		intron_variant		1	NM_002350.4	ENSP00000428924.1
LYN	ENST00000520220.6	c.-5-4314A>G		intron_variant		1		ENSP00000428424.1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44253 AN: 152020 Hom.: 8485 Cov.: 32

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.0254

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.291 AC: 44315 AN: 152138 Hom.: 8508 Cov.: 32 AF XY: 0.283 AC XY: 21041 AN XY: 74380

Gnomad4 AFR AF: 0.548

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.0255

Gnomad4 SAS AF: 0.151

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.271

Alfa AF: 0.103 Hom.: 136

Bravo AF: 0.309

Asia WGS AF: 0.114 AC: 398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.5
DANN	Benign	0.43

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

Publications

LitVar

Other links and lift over

dbSNP: rs2100245; hg19: chr8-56850100;