2-175994013-T-C

Position:

• chr2-175994013-T-C

Variant summary

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

The NM_030650.3(LNPK):​c.28-790A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 209,626 control chromosomes in the GnomAD database, including 3,608 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 0.16 (2408 hom., cov: 32)
  • Exomes 𝑓: 0.20 (1200 hom.)
• Consequence: LNPK NM_030650.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21

Genes affected

LNPK (HGNC:21610): (lunapark, ER junction formation factor) Enables identical protein binding activity. Involved in endoplasmic reticulum tubular network maintenance and positive regulation of endoplasmic reticulum tubular network organization. Located in endoplasmic reticulum tubular network membrane and nucleoplasm. Is integral component of endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

LNPK (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LNPK	NM_030650.3	c.28-790A>G		intron_variant		ENST00000272748.9	NP_085153.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LNPK	ENST00000272748.9	c.28-790A>G		intron_variant		1	NM_030650.3	ENSP00000272748.4

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24891 AN: 151956 Hom.: 2414 Cov.: 32

Gnomad AFR AF: 0.0819

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.223

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.321

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.166

GnomAD4 exome AF: 0.202 AC: 11617 AN: 57552 Hom.: 1200 AF XY: 0.202 AC XY: 5596 AN XY: 27718

Gnomad4 AFR exome AF: 0.0735

Gnomad4 AMR exome AF: 0.136

Gnomad4 ASJ exome AF: 0.223

Gnomad4 EAS exome AF: 0.232

Gnomad4 SAS exome AF: 0.400

Gnomad4 FIN exome AF: 0.111

Gnomad4 NFE exome AF: 0.199

Gnomad4 OTH exome AF: 0.230

GnomAD4 genome AF: 0.164 AC: 24882 AN: 152074 Hom.: 2408 Cov.: 32 AF XY: 0.168 AC XY: 12464 AN XY: 74318

Gnomad4 AFR AF: 0.0817

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.223

Gnomad4 EAS AF: 0.233

Gnomad4 SAS AF: 0.397

Gnomad4 FIN AF: 0.158

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.168

Alfa AF: 0.179 Hom.: 1571

Bravo AF: 0.154

Asia WGS AF: 0.257 AC: 888 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	18
DANN	Benign	0.92

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: rs2885116; hg19: chr2-176858741;