rs12334430

Variant names:

• chr8-55947401-T-A
• rs12334430
• NM_002350.4:c.179-217T>A

Variant summary

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

The NM_002350.4(LYN):​c.179-217T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 152,168 control chromosomes in the GnomAD database, including 7,421 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 0.27 (7421 hom., cov: 33)
• Consequence: LYN NM_002350.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.35
• Publications: 7 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.508 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYN	NM_002350.4	c.179-217T>A		intron_variant	Intron 3 of 12	ENST00000519728.6	NP_002341.1
LYN	NM_001111097.3	c.116-217T>A		intron_variant	Intron 3 of 12		NP_001104567.1
LYN	XM_011517529.4	c.-89-217T>A		intron_variant	Intron 2 of 11		XP_011515831.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LYN	ENST00000519728.6	c.179-217T>A		intron_variant	Intron 3 of 12	1	NM_002350.4	ENSP00000428924.1
LYN	ENST00000520220.6	c.116-217T>A		intron_variant	Intron 3 of 12	1		ENSP00000428424.1
LYN	ENST00000520050.1	c.179-217T>A		intron_variant	Intron 3 of 5	4		ENSP00000428313.1

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41169 AN: 152050 Hom.: 7394 Cov.: 33

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.0248

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.0997

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.271 AC: 41239 AN: 152168 Hom.: 7421 Cov.: 33 AF XY: 0.262 AC XY: 19509 AN XY: 74408

African (AFR) AF: 0.513 AC: 21295 AN: 41478

American (AMR) AF: 0.210 AC: 3205 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 806 AN: 3470

East Asian (EAS) AF: 0.0249 AC: 129 AN: 5188

South Asian (SAS) AF: 0.140 AC: 677 AN: 4824

European-Finnish (FIN) AF: 0.0997 AC: 1057 AN: 10606

Middle Eastern (MID) AF: 0.346 AC: 101 AN: 292

European-Non Finnish (NFE) AF: 0.193 AC: 13149 AN: 67996

Other (OTH) AF: 0.259 AC: 547 AN: 2108

Alfa AF: 0.234 Hom.: 680

Bravo AF: 0.289

Asia WGS AF: 0.105 AC: 364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.17
DANN	Benign	0.086
PhyloP100		-2.4
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: rs12334430; hg19: chr8-56859960;