rs2304397

Positions:

• chr8-142775790-G-A
• chr8-142775790-G-C

Variant summary

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

The NM_177477.4(LYNX1):​c.53-96C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 1,536,342 control chromosomes in the GnomAD database, including 26,364 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 (2083 hom., cov: 34)
  • Exomes 𝑓: 0.18 (24281 hom.)
• Consequence: LYNX1 NM_177477.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0630

Genes affected

LYNX1 (HGNC:29604): (Ly6/neurotoxin 1) This gene encodes a GPI-anchored, cell membrane bound member of the Ly6/uPAR (LU) superfamily of proteins containing the unique three-finger LU domain. This protein interacts with nicotinic acetylcholine receptors (nAChRs), and is thought to function as a modulator of nAChR activity to prevent excessive excitation. Alternatively spliced transcript variants have been found for this gene. Read-through transcription between this gene and the neighboring downstream gene (SLURP2) generates naturally-occurring transcripts (LYNX1-SLURP2) that encode a fusion protein comprised of sequence sharing identity with each individual gene product. [provided by RefSeq, Sep 2017]

LYNX1-SLURP2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LYNX1	NM_177477.4	c.53-96C>T		intron_variant		ENST00000652477.1	NP_803430.1
LYNX1-SLURP2	NM_023946.5	c.53-96C>T		intron_variant			NP_076435.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LYNX1	ENST00000652477.1	c.53-96C>T		intron_variant			NM_177477.4	ENSP00000498325	P1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23404 AN: 152128 Hom.: 2083 Cov.: 34

Gnomad AFR AF: 0.0775

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.138

GnomAD4 exome AF: 0.184 AC: 254918 AN: 1384096 Hom.: 24281 Cov.: 24 AF XY: 0.184 AC XY: 126232 AN XY: 687576

Gnomad4 AFR exome AF: 0.0734

Gnomad4 AMR exome AF: 0.0853

Gnomad4 ASJ exome AF: 0.166

Gnomad4 EAS exome AF: 0.117

Gnomad4 SAS exome AF: 0.158

Gnomad4 FIN exome AF: 0.212

Gnomad4 NFE exome AF: 0.196

Gnomad4 OTH exome AF: 0.171

GnomAD4 genome AF: 0.154 AC: 23403 AN: 152246 Hom.: 2083 Cov.: 34 AF XY: 0.153 AC XY: 11400 AN XY: 74440

Gnomad4 AFR AF: 0.0774

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.212

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.137

Alfa AF: 0.135 Hom.: 383

Bravo AF: 0.141

Asia WGS AF: 0.108 AC: 375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.1
DANN	Benign	0.69

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: rs2304397; hg19: chr8-143857208; COSMIC: COSV59988472;