18-2946293-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+4762G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.92 in 152,228 control chromosomes in the GnomAD database, including 65,084 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 0.92 (65084 hom., cov: 32)
  • Exomes 𝑓: 0.97 (644315 hom.)
  • Failed GnomAD Quality Control
• Consequence: LPIN2 NM_001375808.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.75

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]

(HGNC:):

CHORDC1P4 (HGNC:54688): (CHORDC1 pseudogene 4)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPIN2	NM_001375808.2	c.590+4762G>A		intron_variant		ENST00000677752.1
CHORDC1P4	NR_026659.1	n.331G>A		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPIN2	ENST00000677752.1	c.590+4762G>A		intron_variant			NM_001375808.2	P1
	ENST00000581139.1	n.598G>A		non_coding_transcript_exon_variant	1/1
CHORDC1P4	ENST00000582850.1	n.242G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.920 AC: 139991 AN: 152110 Hom.: 65039 Cov.: 32

Gnomad AFR AF: 0.772

Gnomad AMI AF: 0.981

Gnomad AMR AF: 0.960

Gnomad ASJ AF: 0.966

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.925

Gnomad FIN AF: 0.996

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.981

Gnomad OTH AF: 0.920

GnomAD3 exomes AF: 0.961 AC: 241337 AN: 251088 Hom.: 116394 AF XY: 0.962 AC XY: 130632 AN XY: 135722

Gnomad AFR exome AF: 0.765

Gnomad AMR exome AF: 0.976

Gnomad ASJ exome AF: 0.962

Gnomad EAS exome AF: 0.994

Gnomad SAS exome AF: 0.930

Gnomad FIN exome AF: 0.996

Gnomad NFE exome AF: 0.981

Gnomad OTH exome AF: 0.963

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.973 AC: 1321826 AN: 1358094 Hom.: 644315 Cov.: 25 AF XY: 0.972 AC XY: 662414 AN XY: 681266

Gnomad4 AFR exome AF: 0.761

Gnomad4 AMR exome AF: 0.974

Gnomad4 ASJ exome AF: 0.966

Gnomad4 EAS exome AF: 0.997

Gnomad4 SAS exome AF: 0.929

Gnomad4 FIN exome AF: 0.996

Gnomad4 NFE exome AF: 0.982

Gnomad4 OTH exome AF: 0.962

GnomAD4 genome AF: 0.920 AC: 140096 AN: 152228 Hom.: 65084 Cov.: 32 AF XY: 0.922 AC XY: 68600 AN XY: 74426

Gnomad4 AFR AF: 0.772

Gnomad4 AMR AF: 0.960

Gnomad4 ASJ AF: 0.966

Gnomad4 EAS AF: 0.995

Gnomad4 SAS AF: 0.926

Gnomad4 FIN AF: 0.996

Gnomad4 NFE AF: 0.981

Gnomad4 OTH AF: 0.921

Alfa AF: 0.969 Hom.: 68697

Bravo AF: 0.912

Asia WGS AF: 0.957 AC: 3328 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	4.7
Dann	Benign	0.67

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: rs643507; hg19: chr18-2946291; COSMIC: COSV55236651; COSMIC: COSV55236651;