NM_002350.4:c.383+35A>G

Variant names:

• chr8-55950592-A-G
• rs7813271
• NM_002350.4:c.383+35A>G

Variant summary

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

The NM_002350.4(LYN):​c.383+35A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 1,581,486 control chromosomes in the GnomAD database, including 31,463 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 0.24 (5166 hom., cov: 32)
  • Exomes 𝑓: 0.18 (26297 hom.)
• Consequence: LYN NM_002350.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.536
• Publications: 12 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.393 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.383+35A>G		intron	N/A	NP_002341.1	P07948-1
	LYN	NM_001111097.3		c.320+35A>G		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.383+35A>G		intron	N/A	ENSP00000428924.1	P07948-1
	LYN	ENST00000520220.6	TSL:1	c.320+35A>G		intron	N/A	ENSP00000428424.1	P07948-2
	LYN	ENST00000862998.1		c.383+35A>G		intron	N/A	ENSP00000533057.1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35889 AN: 151954 Hom.: 5150 Cov.: 32

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.0248

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.231

GnomAD2 exomes AF: 0.175 AC: 43850 AN: 250314 AF XY: 0.175

Gnomad AFR exome AF: 0.399

Gnomad AMR exome AF: 0.139

Gnomad ASJ exome AF: 0.251

Gnomad EAS exome AF: 0.0186

Gnomad FIN exome AF: 0.0996

Gnomad NFE exome AF: 0.193

Gnomad OTH exome AF: 0.196

GnomAD4 exome AF: 0.185 AC: 264192 AN: 1429414 Hom.: 26297 Cov.: 25 AF XY: 0.184 AC XY: 131418 AN XY: 712950

African (AFR) AF: 0.400 AC: 13102 AN: 32778

American (AMR) AF: 0.143 AC: 6337 AN: 44372

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 6566 AN: 25918

East Asian (EAS) AF: 0.0328 AC: 1297 AN: 39536

South Asian (SAS) AF: 0.150 AC: 12834 AN: 85370

European-Finnish (FIN) AF: 0.103 AC: 5518 AN: 53384

Middle Eastern (MID) AF: 0.277 AC: 1585 AN: 5716

European-Non Finnish (NFE) AF: 0.190 AC: 205417 AN: 1083034

Other (OTH) AF: 0.195 AC: 11536 AN: 59306

GnomAD4 genome AF: 0.236 AC: 35939 AN: 152072 Hom.: 5166 Cov.: 32 AF XY: 0.229 AC XY: 17021 AN XY: 74318

African (AFR) AF: 0.398 AC: 16489 AN: 41444

American (AMR) AF: 0.191 AC: 2917 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 798 AN: 3470

East Asian (EAS) AF: 0.0248 AC: 129 AN: 5194

South Asian (SAS) AF: 0.141 AC: 677 AN: 4818

European-Finnish (FIN) AF: 0.100 AC: 1058 AN: 10574

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13022 AN: 67974

Other (OTH) AF: 0.228 AC: 483 AN: 2116

Alfa AF: 0.206 Hom.: 2308

Bravo AF: 0.249

Asia WGS AF: 0.0950 AC: 332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.40
PhyloP100		-0.54
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: rs7813271; hg19: chr8-56863151; COSMIC: COSV70205754; COSMIC: COSV70205754;