rs402781

Positions:

• chr10-88766622-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000404459.2(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 ENST00000404459.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.262

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
LIPN	NM_001102469.2	c.535+244C>T		intron_variant		ENST00000404459.2	NP_001095939.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPN	ENST00000404459.2	c.535+244C>T		intron_variant		1	NM_001102469.2	ENSP00000383923	P1
LIPN	ENST00000674982.1	n.2572C>T		non_coding_transcript_exon_variant	4/4

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29347 AN: 151666 Hom.: 2843 Cov.: 31

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.: 31 AF XY: 0.191 AC XY: 14166 AN XY: 74176

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.209

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.0941

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.184

Alfa AF: 0.201 Hom.: 6302

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

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.56

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: rs402781; hg19: chr10-90526379;