chr10-88764786-G-A

Variant names:

• chr10-88764786-G-A
• rs418276
• NM_001102469.2:c.425+178G>A

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.425+178G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 151,768 control chromosomes in the GnomAD database, including 4,434 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.24 (4434 hom., cov: 32)
• Consequence: LIPN NM_001102469.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.699
• 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: 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 10-88764786-G-A is Benign according to our data. Variant chr10-88764786-G-A is described in ClinVar as Benign. ClinVar VariationId is 1257628.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.352 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.425+178G>A		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.425+178G>A		intron	N/A	ENSP00000383923.1
	LIPN	ENST00000674982.1		n.736G>A		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35992 AN: 151650 Hom.: 4417 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.238 AC: 36051 AN: 151768 Hom.: 4434 Cov.: 32 AF XY: 0.236 AC XY: 17536 AN XY: 74164

African (AFR) AF: 0.259 AC: 10740 AN: 41388

American (AMR) AF: 0.267 AC: 4065 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 919 AN: 3466

East Asian (EAS) AF: 0.365 AC: 1872 AN: 5122

South Asian (SAS) AF: 0.273 AC: 1314 AN: 4812

European-Finnish (FIN) AF: 0.153 AC: 1619 AN: 10576

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14762 AN: 67878

Other (OTH) AF: 0.227 AC: 478 AN: 2108

Alfa AF: 0.235 Hom.: 683

Bravo AF: 0.247

Asia WGS AF: 0.311 AC: 1084 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.8
DANN	Benign	0.75
PhyloP100		0.70
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: rs418276; hg19: chr10-90524543;