rs907423

Variant names:

• chr8-55971059-G-C
• rs907423
• NM_002350.4:c.1050+1266G>C

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+1266G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 152,052 control chromosomes in the GnomAD database, including 14,596 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 0.43 (14596 hom., cov: 32)
• Consequence: LYN NM_002350.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.165
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002350.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYN	NM_002350.4	MANE Select	c.1050+1266G>C		intron	N/A	NP_002341.1	P07948-1
	LYN	NM_001111097.3		c.987+1266G>C		intron	N/A	NP_001104567.1	P07948-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYN	ENST00000519728.6	TSL:1 MANE Select	c.1050+1266G>C		intron	N/A	ENSP00000428924.1	P07948-1
	LYN	ENST00000520220.6	TSL:1	c.987+1266G>C		intron	N/A	ENSP00000428424.1	P07948-2
	LYN	ENST00000862998.1		c.1077+1266G>C		intron	N/A	ENSP00000533057.1

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65593 AN: 151934 Hom.: 14592 Cov.: 32

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.685

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.485

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

GnomAD4 genome AF: 0.432 AC: 65633 AN: 152052 Hom.: 14596 Cov.: 32 AF XY: 0.422 AC XY: 31352 AN XY: 74328

African (AFR) AF: 0.457 AC: 18955 AN: 41462

American (AMR) AF: 0.383 AC: 5852 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 1681 AN: 3470

East Asian (EAS) AF: 0.248 AC: 1283 AN: 5170

South Asian (SAS) AF: 0.289 AC: 1395 AN: 4822

European-Finnish (FIN) AF: 0.345 AC: 3648 AN: 10570

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.456 AC: 31012 AN: 67962

Other (OTH) AF: 0.485 AC: 1025 AN: 2112

Alfa AF: 0.447 Hom.: 1899

Bravo AF: 0.437

Asia WGS AF: 0.283 AC: 988 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.41
PhyloP100		-0.17
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs907423;

hg19: chr8-56883618;