rs188571

Variant names:

• chr10-88763082-G-A
• rs188571
• NM_001102469.2:c.226+777G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001102469.2(LIPN):​c.226+777G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 151,866 control chromosomes in the GnomAD database, including 4,385 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 0.24 (4385 hom., cov: 32)
• Consequence: LIPN NM_001102469.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.337 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.226+777G>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.226+777G>A		intron	N/A	ENSP00000383923.1
	LIPN	ENST00000674982.1		n.359+777G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35833 AN: 151748 Hom.: 4366 Cov.: 32

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.236 AC: 35892 AN: 151866 Hom.: 4385 Cov.: 32 AF XY: 0.235 AC XY: 17445 AN XY: 74204

African (AFR) AF: 0.257 AC: 10660 AN: 41458

American (AMR) AF: 0.267 AC: 4078 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 919 AN: 3472

East Asian (EAS) AF: 0.351 AC: 1801 AN: 5134

South Asian (SAS) AF: 0.260 AC: 1251 AN: 4818

European-Finnish (FIN) AF: 0.155 AC: 1629 AN: 10534

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

European-Non Finnish (NFE) AF: 0.218 AC: 14798 AN: 67892

Other (OTH) AF: 0.226 AC: 476 AN: 2104

Alfa AF: 0.230 Hom.: 513

Bravo AF: 0.245

Asia WGS AF: 0.302 AC: 1052 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.0
DANN	Benign	0.54
PhyloP100		-0.071
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: rs188571; hg19: chr10-90522839;