Genetic Variant NM_001102469.2:c.535+244C>T (chr10-88766622-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001102469.2(LIPN):c.535+244C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 151,784 control chromosomes in the GnomAD database, including 2,852 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.19 ( 2852 hom., cov: 31)

Consequence

LIPN
NM_001102469.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.262

Publications

6 publications found

Variant links:

Genes affected

LIPN (HGNC:23452): (lipase family member N) The gene encodes a lipase that is highly expressed in granular keratinocytes in the epidermis, and plays a role in the differentiation of keratinocytes. Mutations in this gene are associated with lamellar ichthyosis type 4. [provided by RefSeq, Dec 2011]

LIPN Gene-Disease associations (from GenCC):

autosomal recessive congenital ichthyosis 8
Inheritance: AR, Unknown Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
lamellar ichthyosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LIPN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 10-88766622-C-T is Benign according to our data. Variant chr10-88766622-C-T is described in ClinVar as Benign. ClinVar VariationId is 1282002.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPN	NM_001102469.2 link	c.535+244C>T		intron_variant	Intron 5 of 9	ENST00000404459.2	NP_001095939.1	Q5VXI9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPN	ENST00000404459.2 link	c.535+244C>T		intron_variant	Intron 5 of 9	1	NM_001102469.2	ENSP00000383923.1		Q5VXI9
LIPN	ENST00000674982.1 link	n.2572C>T		non_coding_transcript_exon_variant	Exon 4 of 4

Frequencies

GnomAD3 genomes

AF:

0.193

AC:

29347

AN:

151666

Hom.:

2843

Cov.:

show subpopulations

Gnomad AFR

AF:

0.192

Gnomad AMI

AF:

0.191

Gnomad AMR

AF:

0.209

Gnomad ASJ

AF:

0.149

Gnomad EAS

AF:

0.0931

Gnomad SAS

AF:

0.125

Gnomad FIN

AF:

0.191

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.207

Gnomad OTH

AF:

0.186

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

GnomAD4 genome

AF:

0.194

AC:

29384

AN:

151784

Hom.:

2852

Cov.:

AF XY:

0.191

AC XY:

14166

AN XY:

74176

show subpopulations

African (AFR)

AF:

0.192

AC:

7963

AN:

41440

American (AMR)

AF:

0.209

AC:

3173

AN:

15200

Ashkenazi Jewish (ASJ)

AF:

0.149

AC:

518

AN:

3468

East Asian (EAS)

AF:

0.0941

AC:

484

AN:

5144

South Asian (SAS)

AF:

0.125

AC:

601

AN:

4816

European-Finnish (FIN)

AF:

0.191

AC:

2018

AN:

10564

Middle Eastern (MID)

AF:

0.122

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.207

AC:

14029

AN:

67840

Other (OTH)

AF:

0.184

AC:

389

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1228

2457

3685

4914

6142

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

312

624

936

1248

1560

<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:

0.203

Hom.:

13371

Bravo

AF:

0.199

Asia WGS

AF:

0.131

AC:

457

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.2

(source)

DANN

Benign

0.56

PhyloP100

-0.26

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over