NM_002350.4:c.-5-242C>T

Variant names:

• chr8-55941613-C-T
• rs16922459
• NM_002350.4:c.-5-242C>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.-5-242C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 152,064 control chromosomes in the GnomAD database, including 1,889 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 0.15 (1889 hom., cov: 32)
• Consequence: LYN NM_002350.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.70
• Publications: 7 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYN	NM_002350.4	c.-5-242C>T		intron_variant	Intron 1 of 12	ENST00000519728.6	NP_002341.1
LYN	NM_001111097.3	c.-5-242C>T		intron_variant	Intron 1 of 12		NP_001104567.1
LYN	XM_011517529.4	c.-135-4835C>T		intron_variant	Intron 1 of 11		XP_011515831.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LYN	ENST00000519728.6	c.-5-242C>T		intron_variant	Intron 1 of 12	1	NM_002350.4	ENSP00000428924.1
LYN	ENST00000520220.6	c.-5-242C>T		intron_variant	Intron 1 of 12	1		ENSP00000428424.1
LYN	ENST00000520050.1	c.-5-242C>T		intron_variant	Intron 1 of 5	4		ENSP00000428313.1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22916 AN: 151946 Hom.: 1887 Cov.: 32

Gnomad AFR AF: 0.167

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0830

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.151 AC: 22924 AN: 152064 Hom.: 1889 Cov.: 32 AF XY: 0.146 AC XY: 10821 AN XY: 74334

African (AFR) AF: 0.167 AC: 6912 AN: 41470

American (AMR) AF: 0.138 AC: 2112 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.223 AC: 775 AN: 3470

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5178

South Asian (SAS) AF: 0.117 AC: 564 AN: 4806

European-Finnish (FIN) AF: 0.0830 AC: 876 AN: 10558

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 11012 AN: 67990

Other (OTH) AF: 0.156 AC: 329 AN: 2112

Alfa AF: 0.159 Hom.: 5576

Bravo AF: 0.155

Asia WGS AF: 0.0610 AC: 213 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.013
DANN	Benign	0.67
PhyloP100		-2.7
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: rs16922459; hg19: chr8-56854172;