10-88760926-A-G

Variant names:

• chr10-88760926-A-G
• rs391683
• NM_001102469.2:c.-8-472A>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.-8-472A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.789 in 152,098 control chromosomes in the GnomAD database, including 48,207 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 0.79 (48207 hom., cov: 32)
• Consequence: LIPN NM_001102469.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0120
• 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: 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LIPN	NM_001102469.2	MANE Select	c.-8-472A>G		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.-8-472A>G		intron	N/A	ENSP00000383923.1	Q5VXI9
	LIPN	ENST00000674982.1		n.126-472A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.789 AC: 119894 AN: 151980 Hom.: 48138 Cov.: 32

Gnomad AFR AF: 0.935

Gnomad AMI AF: 0.851

Gnomad AMR AF: 0.808

Gnomad ASJ AF: 0.767

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.824

Gnomad FIN AF: 0.723

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.688

Gnomad OTH AF: 0.790

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

GnomAD4 genome AF: 0.789 AC: 120023 AN: 152098 Hom.: 48207 Cov.: 32 AF XY: 0.792 AC XY: 58899 AN XY: 74334

African (AFR) AF: 0.935 AC: 38843 AN: 41536

American (AMR) AF: 0.808 AC: 12340 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.767 AC: 2663 AN: 3472

East Asian (EAS) AF: 0.997 AC: 5147 AN: 5164

South Asian (SAS) AF: 0.824 AC: 3976 AN: 4824

European-Finnish (FIN) AF: 0.723 AC: 7642 AN: 10566

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.688 AC: 46728 AN: 67954

Other (OTH) AF: 0.792 AC: 1675 AN: 2114

Alfa AF: 0.774 Hom.: 6792

Bravo AF: 0.803

Asia WGS AF: 0.923 AC: 3210 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.5
DANN	Benign	0.37
PhyloP100		-0.012

Splicing

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

Other links and lift over

dbSNP: rs391683; hg19: chr10-90520683;