8-55969624-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002350.4(LYN):c.974-93A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 930,604 control chromosomes in the GnomAD database, including 85,906 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 0.43 (14595 hom., cov: 33)
  • Exomes 𝑓: 0.42 (71311 hom.)
• Consequence: LYN NM_002350.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LYN	NM_002350.4	c.974-93A>G		intron_variant		ENST00000519728.6
LYN	NM_001111097.3	c.911-93A>G		intron_variant
LYN	XM_011517529.4	c.707-93A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LYN	ENST00000519728.6	c.974-93A>G		intron_variant		1	NM_002350.4	P4
LYN	ENST00000520220.6	c.911-93A>G		intron_variant		1		A1
LYN	ENST00000420292.1	n.382-93A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65618 AN: 151988 Hom.: 14591 Cov.: 33

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.685

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.485

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.456

Gnomad OTH AF: 0.484

GnomAD4 exome AF: 0.420 AC: 326926 AN: 778498 Hom.: 71311 AF XY: 0.418 AC XY: 172118 AN XY: 411524

Gnomad4 AFR exome AF: 0.456

Gnomad4 AMR exome AF: 0.280

Gnomad4 ASJ exome AF: 0.513

Gnomad4 EAS exome AF: 0.261

Gnomad4 SAS exome AF: 0.303

Gnomad4 FIN exome AF: 0.352

Gnomad4 NFE exome AF: 0.459

Gnomad4 OTH exome AF: 0.439

GnomAD4 genome AF: 0.432 AC: 65657 AN: 152106 Hom.: 14595 Cov.: 33 AF XY: 0.422 AC XY: 31370 AN XY: 74342

Gnomad4 AFR AF: 0.457

Gnomad4 AMR AF: 0.383

Gnomad4 ASJ AF: 0.485

Gnomad4 EAS AF: 0.247

Gnomad4 SAS AF: 0.291

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.456

Gnomad4 OTH AF: 0.485

Alfa AF: 0.413 Hom.: 5903

Bravo AF: 0.437

Asia WGS AF: 0.284 AC: 989 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.24
Dann	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs1027987; hg19: chr8-56882183; COSMIC: COSV70205760;