18-2987786-T-G

Position:

• chr18-2987786-T-G

Variant summary

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

The NM_001375808.2(LPIN2):​c.-10+25301A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.943 in 152,128 control chromosomes in the GnomAD database, including 67,913 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 0.94 (67913 hom., cov: 30)
• Consequence: LPIN2 NM_001375808.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.501

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPIN2	NM_001375808.2	c.-10+25301A>C		intron_variant		ENST00000677752.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPIN2	ENST00000677752.1	c.-10+25301A>C		intron_variant			NM_001375808.2	P1
LPIN2	ENST00000261596.9	c.-10+23932A>C		intron_variant		1		P1
LPIN2	ENST00000697039.1	c.-10+25301A>C		intron_variant
LPIN2	ENST00000697040.1	c.-10+25251A>C		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.943 AC: 143331 AN: 152012 Hom.: 67868 Cov.: 30

Gnomad AFR AF: 0.843

Gnomad AMI AF: 0.981

Gnomad AMR AF: 0.970

Gnomad ASJ AF: 0.968

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.943

Gnomad FIN AF: 0.996

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.983

Gnomad OTH AF: 0.946

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

GnomAD4 genome AF: 0.943 AC: 143430 AN: 152128 Hom.: 67913 Cov.: 30 AF XY: 0.944 AC XY: 70176 AN XY: 74366

Gnomad4 AFR AF: 0.843

Gnomad4 AMR AF: 0.970

Gnomad4 ASJ AF: 0.968

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.943

Gnomad4 FIN AF: 0.996

Gnomad4 NFE AF: 0.983

Gnomad4 OTH AF: 0.947

Alfa AF: 0.964 Hom.: 14596

Bravo AF: 0.938

Asia WGS AF: 0.967 AC: 3365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.2
DANN	Benign	0.60

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: rs3934426; hg19: chr18-2987784;