rs1980042

Variant names:

• chr8-55900083-A-G
• rs1980042
• NM_002350.4:c.-6+19980A>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+19980A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 152,000 control chromosomes in the GnomAD database, including 15,109 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 0.44 (15109 hom., cov: 32)
• Consequence: LYN NM_002350.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.193
• Publications: 1 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.541 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+19980A>G		intron	N/A	NP_002341.1
	LYN	NM_001111097.3		c.-6+19980A>G		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+19980A>G		intron	N/A	ENSP00000428924.1
	LYN	ENST00000520220.6	TSL:1	c.-6+19980A>G		intron	N/A	ENSP00000428424.1

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66194 AN: 151882 Hom.: 15077 Cov.: 32

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.568

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.436 AC: 66264 AN: 152000 Hom.: 15109 Cov.: 32 AF XY: 0.427 AC XY: 31747 AN XY: 74288

African (AFR) AF: 0.547 AC: 22675 AN: 41432

American (AMR) AF: 0.378 AC: 5758 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 1441 AN: 3472

East Asian (EAS) AF: 0.207 AC: 1069 AN: 5162

South Asian (SAS) AF: 0.328 AC: 1582 AN: 4820

European-Finnish (FIN) AF: 0.330 AC: 3483 AN: 10570

Middle Eastern (MID) AF: 0.548 AC: 161 AN: 294

European-Non Finnish (NFE) AF: 0.422 AC: 28678 AN: 67984

Other (OTH) AF: 0.428 AC: 902 AN: 2108

Alfa AF: 0.428 Hom.: 1887

Bravo AF: 0.444

Asia WGS AF: 0.292 AC: 1018 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.4
DANN	Benign	0.48
PhyloP100		-0.19
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: rs1980042; hg19: chr8-56812642;