Genetic Variant NM_030650.3:c.28-790A>G (chr2-175994013-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.21

Publications

8 publications found

Variant links:

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 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

LNPK links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LNPK	NM_030650.3 link	c.28-790A>G		intron_variant	Intron 2 of 12	ENST00000272748.9	NP_085153.1	Q9C0E8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LNPK	ENST00000272748.9 link	c.28-790A>G		intron_variant	Intron 2 of 12	1	NM_030650.3	ENSP00000272748.4		Q9C0E8-1

Frequencies

GnomAD3 genomes

AF:

0.164

AC:

24891

AN:

151956

Hom.:

2414

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.0735

AC:

AN:

966

American (AMR)

AF:

0.136

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.223

AC:

AN:

328

East Asian (EAS)

AF:

0.232

AC:

AN:

250

South Asian (SAS)

AF:

0.400

AC:

432

AN:

1080

European-Finnish (FIN)

AF:

0.111

AC:

AN:

Middle Eastern (MID)

AF:

0.271

AC:

AN:

European-Non Finnish (NFE)

AF:

0.199

AC:

10529

AN:

52936

Other (OTH)

AF:

0.230

AC:

427

AN:

1860

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

484

969

1453

1938

2422

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

508

1016

1524

2032

2540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.164

AC:

24882

AN:

152074

Hom.:

2408

Cov.:

AF XY:

0.168

AC XY:

12464

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.0817

AC:

3393

AN:

41512

American (AMR)

AF:

0.146

AC:

2224

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.223

AC:

772

AN:

3462

East Asian (EAS)

AF:

0.233

AC:

1205

AN:

5170

South Asian (SAS)

AF:

0.397

AC:

1913

AN:

4816

European-Finnish (FIN)

AF:

0.158

AC:

1671

AN:

10564

Middle Eastern (MID)

AF:

0.300

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.191

AC:

12997

AN:

67960

Other (OTH)

AF:

0.168

AC:

355

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1050

2101

3151

4202

5252

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

284

568

852

1136

1420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.179

Hom.:

1715

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

(source)

DANN

Benign

0.92

PhyloP100

1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over