NM_001102469.2:c.536-371A>G

Variant names:

• chr10-88768421-A-G
• rs444386
• NM_001102469.2:c.536-371A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001102469.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPN	NM_001102469.2	MANE Select	c.536-371A>G		intron	N/A	NP_001095939.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPN	ENST00000404459.2	TSL:1 MANE Select	c.536-371A>G		intron	N/A	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

African (AFR) AF: 0.202 AC: 8364 AN: 41380

American (AMR) AF: 0.316 AC: 4800 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1097 AN: 3470

East Asian (EAS) AF: 0.359 AC: 1833 AN: 5110

South Asian (SAS) AF: 0.334 AC: 1605 AN: 4812

European-Finnish (FIN) AF: 0.219 AC: 2314 AN: 10572

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.258 AC: 17508 AN: 67830

Other (OTH) AF: 0.252 AC: 533 AN: 2112

Alfa AF: 0.263 Hom.: 3253

Bravo AF: 0.259

Asia WGS AF: 0.344 AC: 1198 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.3
DANN	Benign	0.62
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs444386; hg19: chr10-90528178;