rs2667978

chr8-55985392-A-G

Variant summary

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

The NM_002350.4(LYN):c.1051-12954A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,218 control chromosomes in the GnomAD database, including 2,630 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 0.18 (2630 hom., cov: 32)
• Consequence: LYN NM_002350.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0560

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LYN	NM_002350.4	c.1051-12954A>G		intron_variant		ENST00000519728.6
LYN	NM_001111097.3	c.988-12954A>G		intron_variant
LYN	XM_011517529.4	c.784-12954A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LYN	ENST00000519728.6	c.1051-12954A>G		intron_variant		1	NM_002350.4	P4
LYN	ENST00000520220.6	c.988-12954A>G		intron_variant		1		A1
LYN	ENST00000420292.1	n.459-12954A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27046 AN: 152100 Hom.: 2621 Cov.: 32

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.375

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.178 AC: 27084 AN: 152218 Hom.: 2630 Cov.: 32 AF XY: 0.174 AC XY: 12957 AN XY: 74436

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.202

Alfa AF: 0.211 Hom.: 4718

Bravo AF: 0.178

Asia WGS AF: 0.0590 AC: 205 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	2.5
Dann	Benign	0.58

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: rs2667978; hg19: chr8-56897951;