8-56009113-C-T

Variant names:

• chr8-56009113-C-T
• rs7824121
• NM_002350.4:c.1337-795C>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.1337-795C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.897 in 152,282 control chromosomes in the GnomAD database, including 61,587 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 0.90 (61587 hom., cov: 33)
• Consequence: LYN NM_002350.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.333
• Publications: 5 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.967 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYN	NM_002350.4	MANE Select	c.1337-795C>T		intron	N/A	NP_002341.1
	LYN	NM_001111097.3		c.1274-795C>T		intron	N/A	NP_001104567.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LYN	ENST00000519728.6	TSL:1 MANE Select	c.1337-795C>T		intron	N/A	ENSP00000428924.1
	LYN	ENST00000520220.6	TSL:1	c.1274-795C>T		intron	N/A	ENSP00000428424.1

Frequencies

GnomAD3 genomes AF: 0.897 AC: 136460 AN: 152164 Hom.: 61522 Cov.: 33

Gnomad AFR AF: 0.975

Gnomad AMI AF: 0.953

Gnomad AMR AF: 0.883

Gnomad ASJ AF: 0.887

Gnomad EAS AF: 0.973

Gnomad SAS AF: 0.801

Gnomad FIN AF: 0.799

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.867

Gnomad OTH AF: 0.920

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

GnomAD4 genome AF: 0.897 AC: 136582 AN: 152282 Hom.: 61587 Cov.: 33 AF XY: 0.891 AC XY: 66348 AN XY: 74452

African (AFR) AF: 0.975 AC: 40528 AN: 41566

American (AMR) AF: 0.883 AC: 13503 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.887 AC: 3081 AN: 3472

East Asian (EAS) AF: 0.973 AC: 5056 AN: 5196

South Asian (SAS) AF: 0.801 AC: 3861 AN: 4820

European-Finnish (FIN) AF: 0.799 AC: 8460 AN: 10588

Middle Eastern (MID) AF: 0.949 AC: 279 AN: 294

European-Non Finnish (NFE) AF: 0.867 AC: 59001 AN: 68026

Other (OTH) AF: 0.920 AC: 1944 AN: 2114

Alfa AF: 0.906 Hom.: 38585

Bravo AF: 0.911

Asia WGS AF: 0.894 AC: 3108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.41
DANN	Benign	0.44
PhyloP100		-0.33
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: rs7824121; hg19: chr8-56921672;