rs200130790

Variant names:

• chr18-2937686-G-A
• rs200130790
• NM_001375808.2:c.1168+6C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS1

The NM_001375808.2(LPIN2):​c.1168+6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00032 in 1,612,314 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00033 (0 hom.)
• Consequence: LPIN2 NM_001375808.2 splice_region, intron
• Scores: Splicing: ADA: 0.00005704
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:5 B:3
• Conservation: PhyloP100: -0.324
• Publications: 0 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]

LPIN2 Gene-Disease associations (from GenCC):

• Majeed syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000263 (40/151890) while in subpopulation NFE AF = 0.000427 (29/67968). AF 95% confidence interval is 0.000304. There are 0 homozygotes in GnomAd4. There are 14 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375808.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPIN2	NM_001375808.2	MANE Select	c.1168+6C>T		splice_region intron	N/A	NP_001362737.1	Q92539
	LPIN2	NM_001375809.1		c.1168+6C>T		splice_region intron	N/A	NP_001362738.1	Q92539
	LPIN2	NM_014646.2		c.1168+6C>T		splice_region intron	N/A	NP_055461.1	Q92539

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPIN2	ENST00000677752.1	MANE Select	c.1168+6C>T		splice_region intron	N/A	ENSP00000504857.1	Q92539
	LPIN2	ENST00000261596.9	TSL:1	c.1168+6C>T		splice_region intron	N/A	ENSP00000261596.4	Q92539
	LPIN2	ENST00000697040.1		c.1168+6C>T		splice_region intron	N/A	ENSP00000513062.1	Q92539

Frequencies

GnomAD3 genomes AF: 0.000264 AC: 40 AN: 151772 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000170

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000427

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000295 AC: 74 AN: 250712 AF XY: 0.000280

Gnomad AFR exome AF: 0.0000621

Gnomad AMR exome AF: 0.000260

Gnomad ASJ exome AF: 0.0000993

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000494

Gnomad OTH exome AF: 0.00114

GnomAD4 exome AF: 0.000326 AC: 476 AN: 1460424 Hom.: 0 Cov.: 33 AF XY: 0.000318 AC XY: 231 AN XY: 726590

African (AFR) AF: 0.000120 AC: 4 AN: 33446

American (AMR) AF: 0.000268 AC: 12 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86214

European-Finnish (FIN) AF: 0.0000941 AC: 5 AN: 53110

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.000391 AC: 434 AN: 1110984

Other (OTH) AF: 0.000298 AC: 18 AN: 60360

GnomAD4 genome AF: 0.000263 AC: 40 AN: 151890 Hom.: 0 Cov.: 32 AF XY: 0.000189 AC XY: 14 AN XY: 74222

African (AFR) AF: 0.000169 AC: 7 AN: 41414

American (AMR) AF: 0.000197 AC: 3 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10500

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000427 AC: 29 AN: 67968

Other (OTH) AF: 0.000474 AC: 1 AN: 2110

Alfa AF: 0.000340 Hom.: 0

Bravo AF: 0.000238

EpiCase AF: 0.000491

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	3	not provided (4)
-	2	-	Majeed syndrome (2)
-	1	-	Autoinflammatory syndrome (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.2
DANN	Benign	0.59
PhyloP100		-0.32

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000057
dbscSNV1_RF	Benign	0.014
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: rs200130790; hg19: chr18-2937684;