rs2667972

Positions:

• chr8-55994102-C-T

Variant summary

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

The NM_002350.4(LYN):​c.1051-4244C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 151,940 control chromosomes in the GnomAD database, including 2,205 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 0.15 (2205 hom., cov: 32)
• Consequence: LYN NM_002350.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.120

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYN	NM_002350.4	c.1051-4244C>T		intron_variant		ENST00000519728.6	NP_002341.1
LYN	NM_001111097.3	c.988-4244C>T		intron_variant			NP_001104567.1
LYN	XM_011517529.4	c.784-4244C>T		intron_variant			XP_011515831.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYN	ENST00000519728.6	c.1051-4244C>T		intron_variant		1	NM_002350.4	ENSP00000428924	P4
LYN	ENST00000520220.6	c.988-4244C>T		intron_variant		1		ENSP00000428424	A1
LYN	ENST00000420292.1	n.459-4244C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22274 AN: 151822 Hom.: 2204 Cov.: 32

Gnomad AFR AF: 0.0357

Gnomad AMI AF: 0.375

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0990

Gnomad FIN AF: 0.164

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.147 AC: 22272 AN: 151940 Hom.: 2205 Cov.: 32 AF XY: 0.143 AC XY: 10616 AN XY: 74222

Gnomad4 AFR AF: 0.0357

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0993

Gnomad4 FIN AF: 0.164

Gnomad4 NFE AF: 0.210

Gnomad4 OTH AF: 0.178

Alfa AF: 0.168 Hom.: 322

Bravo AF: 0.143

Asia WGS AF: 0.0510 AC: 177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.5
DANN	Benign	0.64

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: rs2667972; hg19: chr8-56906661;