chr8-55950592-A-G

Position:

• chr8-55950592-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYN	NM_002350.4	c.383+35A>G		intron_variant		ENST00000519728.6	NP_002341.1
LYN	NM_001111097.3	c.320+35A>G		intron_variant			NP_001104567.1
LYN	XM_011517529.4	c.116+35A>G		intron_variant			XP_011515831.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYN	ENST00000519728.6	c.383+35A>G		intron_variant		1	NM_002350.4	ENSP00000428924	P4
LYN	ENST00000520220.6	c.320+35A>G		intron_variant		1		ENSP00000428424	A1
LYN	ENST00000520050.1	c.383+35A>G		intron_variant		4		ENSP00000428313

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

GnomAD3 exomes AF: 0.175 AC: 43850 AN: 250314 Hom.: 4687 AF XY: 0.175 AC XY: 23628 AN XY: 135304

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 SAS exome AF: 0.150

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

Gnomad4 AFR exome AF: 0.400

Gnomad4 AMR exome AF: 0.143

Gnomad4 ASJ exome AF: 0.253

Gnomad4 EAS exome AF: 0.0328

Gnomad4 SAS exome AF: 0.150

Gnomad4 FIN exome AF: 0.103

Gnomad4 NFE exome AF: 0.190

Gnomad4 OTH exome AF: 0.195

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

Gnomad4 AFR AF: 0.398

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.230

Gnomad4 EAS AF: 0.0248

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.100

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.228

Alfa AF: 0.204 Hom.: 2072

Bravo AF: 0.249

Asia WGS AF: 0.0950 AC: 332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.40

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

Publications

LitVar

Other links and lift over

dbSNP: rs7813271; hg19: chr8-56863151; COSMIC: COSV70205754; COSMIC: COSV70205754;