rs4738466

Variant names:

• chr8-55998142-G-A
• rs4738466
• NM_002350.4:c.1051-204G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-55998142-G-A
• chr8-55998142-G-C
• chr8-55998142-G-T

Variant summary

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

The NM_002350.4(LYN):​c.1051-204G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.885 in 151,590 control chromosomes in the GnomAD database, including 59,642 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 0.89 (59642 hom., cov: 28)
• Consequence: LYN NM_002350.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0880
• Publications: 5 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYN	NM_002350.4	c.1051-204G>A		intron_variant	Intron 10 of 12	ENST00000519728.6	NP_002341.1
LYN	NM_001111097.3	c.988-204G>A		intron_variant	Intron 10 of 12		NP_001104567.1
LYN	XM_011517529.4	c.784-204G>A		intron_variant	Intron 9 of 11		XP_011515831.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LYN	ENST00000519728.6	c.1051-204G>A		intron_variant	Intron 10 of 12	1	NM_002350.4	ENSP00000428924.1
LYN	ENST00000520220.6	c.988-204G>A		intron_variant	Intron 10 of 12	1		ENSP00000428424.1
LYN	ENST00000420292.1	n.459-204G>A		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.885 AC: 134107 AN: 151474 Hom.: 59585 Cov.: 28

Gnomad AFR AF: 0.937

Gnomad AMI AF: 0.953

Gnomad AMR AF: 0.878

Gnomad ASJ AF: 0.867

Gnomad EAS AF: 0.973

Gnomad SAS AF: 0.802

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.867

Gnomad OTH AF: 0.915

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

GnomAD4 genome AF: 0.885 AC: 134219 AN: 151590 Hom.: 59642 Cov.: 28 AF XY: 0.880 AC XY: 65182 AN XY: 74036

African (AFR) AF: 0.937 AC: 38768 AN: 41382

American (AMR) AF: 0.878 AC: 13377 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.867 AC: 3011 AN: 3472

East Asian (EAS) AF: 0.973 AC: 5040 AN: 5180

South Asian (SAS) AF: 0.803 AC: 3857 AN: 4804

European-Finnish (FIN) AF: 0.802 AC: 8300 AN: 10354

Middle Eastern (MID) AF: 0.945 AC: 276 AN: 292

European-Non Finnish (NFE) AF: 0.867 AC: 58790 AN: 67846

Other (OTH) AF: 0.914 AC: 1931 AN: 2112

Alfa AF: 0.878 Hom.: 74034

Bravo AF: 0.897

Asia WGS AF: 0.895 AC: 3112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.20
DANN	Benign	0.38
PhyloP100		-0.088
Mutation Taster		=6/94	disease causing

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: rs4738466; hg19: chr8-56910701;