chr8-55888438-C-T

Variant names:

• chr8-55888438-C-T
• rs333616
• NM_002350.4:c.-6+8335C>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+8335C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.693 in 152,014 control chromosomes in the GnomAD database, including 38,342 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 (38342 hom., cov: 31)
• Consequence: LYN NM_002350.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 5 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 = 0.913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LYN	NM_002350.4	c.-6+8335C>T		intron_variant	Intron 1 of 12	ENST00000519728.6	NP_002341.1
LYN	NM_001111097.3	c.-6+8335C>T		intron_variant	Intron 1 of 12		NP_001104567.1
LYN	XM_011517529.4	c.-136+8335C>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+8335C>T		intron_variant	Intron 1 of 12	1	NM_002350.4	ENSP00000428924.1
LYN	ENST00000520220.6	c.-6+8335C>T		intron_variant	Intron 1 of 12	1		ENSP00000428424.1

Frequencies

GnomAD3 genomes AF: 0.693 AC: 105231 AN: 151896 Hom.: 38280 Cov.: 31

Gnomad AFR AF: 0.921

Gnomad AMI AF: 0.403

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.662

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.675

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

GnomAD4 genome AF: 0.693 AC: 105351 AN: 152014 Hom.: 38342 Cov.: 31 AF XY: 0.699 AC XY: 51954 AN XY: 74290

African (AFR) AF: 0.921 AC: 38217 AN: 41490

American (AMR) AF: 0.668 AC: 10199 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 2106 AN: 3472

East Asian (EAS) AF: 0.820 AC: 4230 AN: 5158

South Asian (SAS) AF: 0.670 AC: 3232 AN: 4824

European-Finnish (FIN) AF: 0.662 AC: 6984 AN: 10550

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.566 AC: 38420 AN: 67936

Other (OTH) AF: 0.679 AC: 1433 AN: 2112

Alfa AF: 0.593 Hom.: 43923

Bravo AF: 0.704

Asia WGS AF: 0.752 AC: 2617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.17
DANN	Benign	0.68
PhyloP100		-1.0
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: rs333616; hg19: chr8-56800997;