8-55963732-T-C

Variant names:

• chr8-55963732-T-C
• rs907425
• NM_002350.4:c.791-2983T>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.791-2983T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 152,140 control chromosomes in the GnomAD database, including 20,435 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 0.50 (20435 hom., cov: 33)
• Consequence: LYN NM_002350.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.145
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.663 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.791-2983T>C		intron	N/A	NP_002341.1
	LYN	NM_001111097.3		c.728-2983T>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.791-2983T>C		intron	N/A	ENSP00000428924.1
	LYN	ENST00000520220.6	TSL:1	c.728-2983T>C		intron	N/A	ENSP00000428424.1
	LYN	ENST00000420292.1	TSL:3	n.199-2983T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76346 AN: 152022 Hom.: 20406 Cov.: 33

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.687

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.359

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.539

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

GnomAD4 genome AF: 0.502 AC: 76425 AN: 152140 Hom.: 20435 Cov.: 33 AF XY: 0.491 AC XY: 36507 AN XY: 74368

African (AFR) AF: 0.670 AC: 27796 AN: 41490

American (AMR) AF: 0.414 AC: 6328 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 1708 AN: 3472

East Asian (EAS) AF: 0.267 AC: 1380 AN: 5178

South Asian (SAS) AF: 0.297 AC: 1434 AN: 4828

European-Finnish (FIN) AF: 0.359 AC: 3793 AN: 10580

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.471 AC: 32044 AN: 67982

Other (OTH) AF: 0.539 AC: 1139 AN: 2114

Alfa AF: 0.499 Hom.: 2520

Bravo AF: 0.514

Asia WGS AF: 0.307 AC: 1072 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.8
DANN	Benign	0.76
PhyloP100		-0.14
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: rs907425; hg19: chr8-56876291;