10-88760926-A-G

Position:

• chr10-88760926-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LIPN	NM_001102469.2	c.-8-472A>G		intron_variant		ENST00000404459.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LIPN	ENST00000404459.2	c.-8-472A>G		intron_variant		1	NM_001102469.2	P1
LIPN	ENST00000674982.1	n.126-472A>G		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.935

Gnomad4 AMR AF: 0.808

Gnomad4 ASJ AF: 0.767

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.824

Gnomad4 FIN AF: 0.723

Gnomad4 NFE AF: 0.688

Gnomad4 OTH AF: 0.792

Alfa AF: 0.768 Hom.: 6456

Bravo AF: 0.803

Asia WGS AF: 0.923 AC: 3210 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs391683; hg19: chr10-90520683;