rs418276

Positions:

• chr10-88764786-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIPN	NM_001102469.2	c.425+178G>A		intron_variant		ENST00000404459.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPN	ENST00000404459.2	c.425+178G>A		intron_variant		1	NM_001102469.2	P1
LIPN	ENST00000674982.1	n.736G>A		non_coding_transcript_exon_variant	4/4

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

Gnomad4 AFR AF: 0.259

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.265

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.227

Alfa AF: 0.236 Hom.: 661

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.8
DANN	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs418276; hg19: chr10-90524543;