rs3745012

Variant names:

• chr18-2920290-G-A
• rs3745012
• NM_001375808.2:c.*3C>T

Your query was ambiguous. Multiple possible variants found:

• chr18-2920290-G-A
• chr18-2920290-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001375808.2(LPIN2):​c.*3C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 1,613,602 control chromosomes in the GnomAD database, including 67,687 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6311 hom., cov: 32)
  • Exomes 𝑓: 0.28 (61376 hom.)
• Consequence: LPIN2 NM_001375808.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -1.63
• Publications: 24 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 18-2920290-G-A is Benign according to our data. Variant chr18-2920290-G-A is described in ClinVar as Benign. ClinVar VariationId is 260433.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

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.*3C>T		3_prime_UTR	Exon 20 of 20	NP_001362737.1	Q92539
	LPIN2	NM_001375809.1		c.*3C>T		3_prime_UTR	Exon 20 of 20	NP_001362738.1	Q92539
	LPIN2	NM_014646.2		c.*3C>T		3_prime_UTR	Exon 20 of 20	NP_055461.1	Q92539

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPIN2	ENST00000677752.1	MANE Select	c.*3C>T		3_prime_UTR	Exon 20 of 20	ENSP00000504857.1	Q92539
	LPIN2	ENST00000261596.9	TSL:1	c.*3C>T		3_prime_UTR	Exon 21 of 21	ENSP00000261596.4	Q92539
	LPIN2	ENST00000697040.1		c.*3C>T		3_prime_UTR	Exon 20 of 20	ENSP00000513062.1	Q92539

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41955 AN: 151970 Hom.: 6294 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.301

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.288

GnomAD2 exomes AF: 0.315 AC: 78969 AN: 250988 AF XY: 0.317

Gnomad AFR exome AF: 0.229

Gnomad AMR exome AF: 0.380

Gnomad ASJ exome AF: 0.218

Gnomad EAS exome AF: 0.599

Gnomad FIN exome AF: 0.256

Gnomad NFE exome AF: 0.257

Gnomad OTH exome AF: 0.295

GnomAD4 exome AF: 0.280 AC: 409882 AN: 1461514 Hom.: 61376 Cov.: 35 AF XY: 0.284 AC XY: 206364 AN XY: 727048

African (AFR) AF: 0.224 AC: 7485 AN: 33478

American (AMR) AF: 0.375 AC: 16786 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 5735 AN: 26134

East Asian (EAS) AF: 0.587 AC: 23315 AN: 39696

South Asian (SAS) AF: 0.404 AC: 34878 AN: 86250

European-Finnish (FIN) AF: 0.261 AC: 13901 AN: 53298

Middle Eastern (MID) AF: 0.277 AC: 1595 AN: 5752

European-Non Finnish (NFE) AF: 0.259 AC: 288496 AN: 1111796

Other (OTH) AF: 0.293 AC: 17691 AN: 60392

GnomAD4 genome AF: 0.276 AC: 42008 AN: 152088 Hom.: 6311 Cov.: 32 AF XY: 0.281 AC XY: 20863 AN XY: 74350

African (AFR) AF: 0.230 AC: 9553 AN: 41492

American (AMR) AF: 0.344 AC: 5257 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 781 AN: 3470

East Asian (EAS) AF: 0.598 AC: 3084 AN: 5156

South Asian (SAS) AF: 0.422 AC: 2034 AN: 4816

European-Finnish (FIN) AF: 0.250 AC: 2651 AN: 10590

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17682 AN: 67960

Other (OTH) AF: 0.294 AC: 621 AN: 2114

Alfa AF: 0.241 Hom.: 3034

Bravo AF: 0.278

Asia WGS AF: 0.502 AC: 1743 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	3	Majeed syndrome (3)
-	-	1	Autoinflammatory syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.65
DANN	Benign	0.51
PhyloP100		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs3745012; hg19: chr18-2920288; COSMIC: COSV54428923; COSMIC: COSV54428923;