rs6474026

Variant names:

• chr8-55880934-T-C
• rs6474026
• NM_002350.4:c.-6+831T>C

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+831T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 152,192 control chromosomes in the GnomAD database, including 2,594 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 (2594 hom., cov: 32)
• Consequence: LYN NM_002350.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• Publications: 11 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.223 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.-6+831T>C		intron	N/A	NP_002341.1
	LYN	NM_001111097.3		c.-6+831T>C		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.-6+831T>C		intron	N/A	ENSP00000428924.1
	LYN	ENST00000520220.6	TSL:1	c.-6+831T>C		intron	N/A	ENSP00000428424.1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27734 AN: 152074 Hom.: 2587 Cov.: 32

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.197

Gnomad OTH AF: 0.186

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

GnomAD4 genome AF: 0.182 AC: 27760 AN: 152192 Hom.: 2594 Cov.: 32 AF XY: 0.179 AC XY: 13305 AN XY: 74404

African (AFR) AF: 0.172 AC: 7144 AN: 41512

American (AMR) AF: 0.158 AC: 2415 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 713 AN: 3472

East Asian (EAS) AF: 0.126 AC: 651 AN: 5184

South Asian (SAS) AF: 0.234 AC: 1131 AN: 4832

European-Finnish (FIN) AF: 0.133 AC: 1409 AN: 10600

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

European-Non Finnish (NFE) AF: 0.197 AC: 13390 AN: 68002

Other (OTH) AF: 0.184 AC: 387 AN: 2106

Alfa AF: 0.192 Hom.: 7747

Bravo AF: 0.181

Asia WGS AF: 0.193 AC: 670 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.5
DANN	Benign	0.53
PhyloP100		-1.0
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: rs6474026; hg19: chr8-56793493;