8-55910632-C-T

Variant names:

• chr8-55910632-C-T
• rs4551325
• NM_002350.4:c.-6+30529C>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.-6+30529C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 152,024 control chromosomes in the GnomAD database, including 35,822 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 0.69 (35822 hom., cov: 32)
• Consequence: LYN NM_002350.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.950
• Publications: 3 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 (EAS) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYN	NM_002350.4	c.-6+30529C>T		intron_variant	Intron 1 of 12	ENST00000519728.6	NP_002341.1
LYN	NM_001111097.3	c.-6+30529C>T		intron_variant	Intron 1 of 12		NP_001104567.1
LYN	XM_011517529.4	c.-136+30529C>T		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+30529C>T		intron_variant	Intron 1 of 12	1	NM_002350.4	ENSP00000428924.1
LYN	ENST00000520220.6	c.-6+30529C>T		intron_variant	Intron 1 of 12	1		ENSP00000428424.1

Frequencies

GnomAD3 genomes AF: 0.685 AC: 104117 AN: 151906 Hom.: 35804 Cov.: 32

Gnomad AFR AF: 0.668

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.684

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.952

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.744

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.674

Gnomad OTH AF: 0.667

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

GnomAD4 genome AF: 0.685 AC: 104187 AN: 152024 Hom.: 35822 Cov.: 32 AF XY: 0.688 AC XY: 51114 AN XY: 74340

African (AFR) AF: 0.667 AC: 27648 AN: 41434

American (AMR) AF: 0.684 AC: 10451 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.628 AC: 2178 AN: 3468

East Asian (EAS) AF: 0.952 AC: 4933 AN: 5180

South Asian (SAS) AF: 0.663 AC: 3200 AN: 4824

European-Finnish (FIN) AF: 0.744 AC: 7847 AN: 10546

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.674 AC: 45815 AN: 67978

Other (OTH) AF: 0.672 AC: 1419 AN: 2112

Alfa AF: 0.673 Hom.: 87871

Bravo AF: 0.682

Asia WGS AF: 0.806 AC: 2801 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.36
DANN	Benign	0.28
PhyloP100		-0.95
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: rs4551325; hg19: chr8-56823191;