18-2948031-C-T

Position:

• chr18-2948031-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001375808.2(LPIN2):​c.590+3024G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,196 control chromosomes in the GnomAD database, including 1,721 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 0.12 (1721 hom., cov: 32)
• Consequence: LPIN2 NM_001375808.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.669

Genes affected

LPIN2 (HGNC:14450): (lipin 2) Mouse studies suggest that this gene functions during normal adipose tissue development and may play a role in human triglyceride metabolism. This gene represents a candidate gene for human lipodystrophy, characterized by loss of body fat, fatty liver, hypertriglyceridemia, and insulin resistance. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPIN2	NM_001375808.2	c.590+3024G>A		intron_variant		ENST00000677752.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPIN2	ENST00000677752.1	c.590+3024G>A		intron_variant			NM_001375808.2	P1

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18690 AN: 152078 Hom.: 1716 Cov.: 32

Gnomad AFR AF: 0.0610

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.146

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

GnomAD4 genome AF: 0.123 AC: 18715 AN: 152196 Hom.: 1721 Cov.: 32 AF XY: 0.127 AC XY: 9451 AN XY: 74408

Gnomad4 AFR AF: 0.0609

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.472

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.149

Alfa AF: 0.128 Hom.: 2671

Bravo AF: 0.126

Asia WGS AF: 0.319 AC: 1108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.3
DANN	Benign	0.76

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: rs10460009; hg19: chr18-2948029;