10-88768421-A-G

Position:

• chr10-88768421-A-G

Variant summary

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

The NM_001102469.2(LIPN):​c.536-371A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 151,702 control chromosomes in the GnomAD database, including 5,083 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 0.25 (5083 hom., cov: 31)
• Consequence: LIPN NM_001102469.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.146

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPN	NM_001102469.2	c.536-371A>G		intron_variant		ENST00000404459.2	NP_001095939.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPN	ENST00000404459.2	c.536-371A>G		intron_variant		1	NM_001102469.2	ENSP00000383923.1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38376 AN: 151584 Hom.: 5071 Cov.: 31

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.253 AC: 38420 AN: 151702 Hom.: 5083 Cov.: 31 AF XY: 0.255 AC XY: 18910 AN XY: 74108

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.316

Gnomad4 ASJ AF: 0.316

Gnomad4 EAS AF: 0.359

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.258

Gnomad4 OTH AF: 0.252

Alfa AF: 0.262 Hom.: 2981

Bravo AF: 0.259

Asia WGS AF: 0.344 AC: 1198 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.3
DANN	Benign	0.62

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: rs444386; hg19: chr10-90528178;