rs402781

Variant names:

• chr10-88766622-C-T
• rs402781
• NM_001102469.2:c.535+244C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001102469.2(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 NM_001102469.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.262
• Publications: 6 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 -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 VariationId 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.

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.535+244C>T		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.535+244C>T		intron	N/A	ENSP00000383923.1	Q5VXI9
	LIPN	ENST00000674982.1		n.2572C>T		non_coding_transcript_exon	Exon 4 of 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

African (AFR) AF: 0.192 AC: 7963 AN: 41440

American (AMR) AF: 0.209 AC: 3173 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 518 AN: 3468

East Asian (EAS) AF: 0.0941 AC: 484 AN: 5144

South Asian (SAS) AF: 0.125 AC: 601 AN: 4816

European-Finnish (FIN) AF: 0.191 AC: 2018 AN: 10564

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14029 AN: 67840

Other (OTH) AF: 0.184 AC: 389 AN: 2110

Alfa AF: 0.203 Hom.: 13371

Bravo AF: 0.199

Asia WGS AF: 0.131 AC: 457 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.56
PhyloP100		-0.26
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs402781;

hg19: chr10-90526379;