10-88761718-GCTATCTATCTATCTATCTATCTAT-GCTATCTATCTATCTATCTATCTATCTATCTAT

Variant names:

• chr10-88761718-G-GCTATCTAT
• rs71022539
• NM_001102469.2:c.108+242_108+249dupCTATCTAT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001102469.2(LIPN):​c.108+242_108+249dupCTATCTAT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.031 (113 hom., cov: 0)
• Consequence: LIPN NM_001102469.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.694
• Publications: 0 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: Unknown, AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
• lamellar ichthyosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0308 (4479/145580) while in subpopulation NFE AF = 0.045 (2970/66032). AF 95% confidence interval is 0.0436. There are 113 homozygotes in GnomAd4. There are 2131 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 113 AR,Unknown gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPN	NM_001102469.2	MANE Select	c.108+242_108+249dupCTATCTAT		intron	N/A	NP_001095939.1	Q5VXI9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPN	ENST00000404459.2	TSL:1 MANE Select	c.108+205_108+206insCTATCTAT		intron	N/A	ENSP00000383923.1	Q5VXI9
	LIPN	ENST00000674982.1		n.241+205_241+206insCTATCTAT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0308 AC: 4479 AN: 145460 Hom.: 113 Cov.: 0

Gnomad AFR AF: 0.00762

Gnomad AMI AF: 0.0209

Gnomad AMR AF: 0.0326

Gnomad ASJ AF: 0.0395

Gnomad EAS AF: 0.000201

Gnomad SAS AF: 0.0316

Gnomad FIN AF: 0.0388

Gnomad MID AF: 0.0258

Gnomad NFE AF: 0.0450

Gnomad OTH AF: 0.0299

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

GnomAD4 genome AF: 0.0308 AC: 4479 AN: 145580 Hom.: 113 Cov.: 0 AF XY: 0.0301 AC XY: 2131 AN XY: 70778

African (AFR) AF: 0.00759 AC: 299 AN: 39378

American (AMR) AF: 0.0325 AC: 465 AN: 14312

Ashkenazi Jewish (ASJ) AF: 0.0395 AC: 133 AN: 3364

East Asian (EAS) AF: 0.000202 AC: 1 AN: 4960

South Asian (SAS) AF: 0.0314 AC: 143 AN: 4554

European-Finnish (FIN) AF: 0.0388 AC: 382 AN: 9838

Middle Eastern (MID) AF: 0.0313 AC: 9 AN: 288

European-Non Finnish (NFE) AF: 0.0450 AC: 2970 AN: 66032

Other (OTH) AF: 0.0296 AC: 59 AN: 1994

Alfa AF: 0.0224 Hom.: 63

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.69
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs71022539; hg19: chr10-90521475;