NM_002350.4:c.-5-9538G>A

Variant names:

• chr8-55932317-G-A
• rs6985030
• NM_002350.4:c.-5-9538G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002350.4(LYN):​c.-5-9538G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,078 control chromosomes in the GnomAD database, including 2,543 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 0.17 (2543 hom., cov: 33)
• Consequence: LYN NM_002350.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.234
• Publications: 6 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.242 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.-5-9538G>A		intron	N/A	NP_002341.1
	LYN	NM_001111097.3		c.-5-9538G>A		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.-5-9538G>A		intron	N/A	ENSP00000428924.1
	LYN	ENST00000520220.6	TSL:1	c.-5-9538G>A		intron	N/A	ENSP00000428424.1

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25902 AN: 151960 Hom.: 2538 Cov.: 33

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.285

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0728

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.171 AC: 25931 AN: 152078 Hom.: 2543 Cov.: 33 AF XY: 0.165 AC XY: 12275 AN XY: 74336

African (AFR) AF: 0.246 AC: 10180 AN: 41424

American (AMR) AF: 0.152 AC: 2321 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 829 AN: 3472

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5192

South Asian (SAS) AF: 0.117 AC: 562 AN: 4824

European-Finnish (FIN) AF: 0.0728 AC: 769 AN: 10564

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10528 AN: 68006

Other (OTH) AF: 0.183 AC: 387 AN: 2114

Alfa AF: 0.167 Hom.: 2570

Bravo AF: 0.179

Asia WGS AF: 0.0680 AC: 236 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.31
DANN	Benign	0.20
PhyloP100		-0.23
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: rs6985030; hg19: chr8-56844876;