rs6983130

Variant names:

• chr8-55880680-A-G
• rs6983130
• NM_002350.4:c.-6+577A>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.-6+577A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.183 in 152,258 control chromosomes in the GnomAD database, including 2,621 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 0.18 (2621 hom., cov: 33)
• Consequence: LYN NM_002350.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 13 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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYN	NM_002350.4	c.-6+577A>G		intron_variant	Intron 1 of 12	ENST00000519728.6	NP_002341.1
LYN	NM_001111097.3	c.-6+577A>G		intron_variant	Intron 1 of 12		NP_001104567.1
LYN	XM_011517529.4	c.-136+577A>G		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.-6+577A>G		intron_variant	Intron 1 of 12	1	NM_002350.4	ENSP00000428924.1
LYN	ENST00000520220.6	c.-6+577A>G		intron_variant	Intron 1 of 12	1		ENSP00000428424.1

Frequencies

GnomAD3 genomes AF: 0.183 AC: 27908 AN: 152140 Hom.: 2614 Cov.: 33

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.183 AC: 27934 AN: 152258 Hom.: 2621 Cov.: 33 AF XY: 0.180 AC XY: 13381 AN XY: 74458

African (AFR) AF: 0.173 AC: 7170 AN: 41552

American (AMR) AF: 0.158 AC: 2418 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 687 AN: 3464

East Asian (EAS) AF: 0.126 AC: 651 AN: 5176

South Asian (SAS) AF: 0.235 AC: 1133 AN: 4826

European-Finnish (FIN) AF: 0.134 AC: 1417 AN: 10610

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13554 AN: 68010

Other (OTH) AF: 0.184 AC: 388 AN: 2112

Alfa AF: 0.183 Hom.: 323

Bravo AF: 0.182

Asia WGS AF: 0.193 AC: 670 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.47
DANN	Benign	0.32
PhyloP100		-1.2
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: rs6983130; hg19: chr8-56793239;