chr18-2946835-T-A

Variant names:

• chr18-2946835-T-A
• rs641287
• NM_001375808.2:c.590+4220A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001375808.2(LPIN2):​c.590+4220A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 372,244 control chromosomes in the GnomAD database, including 75,117 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 0.57 (26940 hom., cov: 32)
  • Exomes 𝑓: 0.65 (48177 hom.)
• Consequence: LPIN2 NM_001375808.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.349
• Publications: 5 publications found

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]

ENSG00000293203 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPIN2	NM_001375808.2	c.590+4220A>T		intron_variant	Intron 4 of 19	ENST00000677752.1	NP_001362737.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPIN2	ENST00000677752.1	c.590+4220A>T		intron_variant	Intron 4 of 19		NM_001375808.2	ENSP00000504857.1

Frequencies

GnomAD3 genomes AF: 0.567 AC: 86039 AN: 151878 Hom.: 26941 Cov.: 32

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.712

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.722

Gnomad MID AF: 0.624

Gnomad NFE AF: 0.710

Gnomad OTH AF: 0.573

GnomAD4 exome AF: 0.653 AC: 143747 AN: 220248 Hom.: 48177 Cov.: 0 AF XY: 0.642 AC XY: 76629 AN XY: 119396

African (AFR) AF: 0.314 AC: 1865 AN: 5934

American (AMR) AF: 0.609 AC: 5003 AN: 8210

Ashkenazi Jewish (ASJ) AF: 0.723 AC: 4250 AN: 5876

East Asian (EAS) AF: 0.384 AC: 3558 AN: 9264

South Asian (SAS) AF: 0.528 AC: 19005 AN: 35998

European-Finnish (FIN) AF: 0.726 AC: 7881 AN: 10862

Middle Eastern (MID) AF: 0.606 AC: 525 AN: 866

European-Non Finnish (NFE) AF: 0.715 AC: 94009 AN: 131516

Other (OTH) AF: 0.653 AC: 7651 AN: 11722

GnomAD4 genome AF: 0.566 AC: 86053 AN: 151996 Hom.: 26940 Cov.: 32 AF XY: 0.564 AC XY: 41878 AN XY: 74314

African (AFR) AF: 0.303 AC: 12537 AN: 41418

American (AMR) AF: 0.584 AC: 8927 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.712 AC: 2470 AN: 3470

East Asian (EAS) AF: 0.359 AC: 1852 AN: 5158

South Asian (SAS) AF: 0.490 AC: 2361 AN: 4822

European-Finnish (FIN) AF: 0.722 AC: 7630 AN: 10570

Middle Eastern (MID) AF: 0.623 AC: 182 AN: 292

European-Non Finnish (NFE) AF: 0.710 AC: 48268 AN: 67960

Other (OTH) AF: 0.571 AC: 1205 AN: 2110

Alfa AF: 0.624 Hom.: 3922

Bravo AF: 0.549

Asia WGS AF: 0.417 AC: 1455 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	4.7
DANN	Benign	0.52
PhyloP100		0.35
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs641287; hg19: chr18-2946833;