chr2-11792047-G-T

Variant names:

• chr2-11792047-G-T
• rs7561070
• NM_001349206.2:c.1806+41G>T

Variant summary

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

The NM_001349206.2(LPIN1):​c.1806+41G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 1,561,184 control chromosomes in the GnomAD database, including 289,607 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (34288 hom., cov: 31)
  • Exomes 𝑓: 0.59 (255319 hom.)
• Consequence: LPIN1 NM_001349206.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.583
• Publications: 14 publications found

Genes affected

LPIN1 (HGNC:13345): (lipin 1) This gene encodes a magnesium-ion-dependent phosphatidic acid phosphohydrolase enzyme that catalyzes the penultimate step in triglyceride synthesis including the dephosphorylation of phosphatidic acid to yield diacylglycerol. Expression of this gene is required for adipocyte differentiation and it also functions as a nuclear transcriptional coactivator with some peroxisome proliferator-activated receptors to modulate expression of other genes involved in lipid metabolism. Mutations in this gene are associated with metabolic syndrome, type 2 diabetes, acute recurrent rhabdomyolysis, and autosomal recessive acute recurrent myoglobinuria (ARARM). This gene is also a candidate for several human lipodystrophy syndromes. [provided by RefSeq, Mar 2017]

LPIN1 Gene-Disease associations (from GenCC):

• myoglobinuria, acute recurrent, autosomal recessive

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
• hereditary recurrent myoglobinuria

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 2-11792047-G-T is Benign according to our data. Variant chr2-11792047-G-T is described in ClinVar as [Benign]. Clinvar id is 262586.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPIN1	NM_001349206.2	c.1806+41G>T		intron_variant	Intron 13 of 20	ENST00000674199.1	NP_001336135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPIN1	ENST00000674199.1	c.1806+41G>T		intron_variant	Intron 13 of 20		NM_001349206.2	ENSP00000501331.1

Frequencies

GnomAD3 genomes AF: 0.650 AC: 98665 AN: 151824 Hom.: 34235 Cov.: 31

Gnomad AFR AF: 0.885

Gnomad AMI AF: 0.580

Gnomad AMR AF: 0.499

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.606

Gnomad OTH AF: 0.589

GnomAD2 exomes AF: 0.539 AC: 130096 AN: 241264 AF XY: 0.537

Gnomad AFR exome AF: 0.895

Gnomad AMR exome AF: 0.361

Gnomad ASJ exome AF: 0.518

Gnomad EAS exome AF: 0.207

Gnomad FIN exome AF: 0.619

Gnomad NFE exome AF: 0.614

Gnomad OTH exome AF: 0.545

GnomAD4 exome AF: 0.593 AC: 835110 AN: 1409238 Hom.: 255319 Cov.: 21 AF XY: 0.587 AC XY: 412756 AN XY: 703174

African (AFR) AF: 0.901 AC: 29382 AN: 32618

American (AMR) AF: 0.375 AC: 16276 AN: 43382

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 13180 AN: 25576

East Asian (EAS) AF: 0.236 AC: 9229 AN: 39158

South Asian (SAS) AF: 0.440 AC: 37120 AN: 84422

European-Finnish (FIN) AF: 0.622 AC: 32702 AN: 52548

Middle Eastern (MID) AF: 0.526 AC: 2967 AN: 5636

European-Non Finnish (NFE) AF: 0.619 AC: 660838 AN: 1067298

Other (OTH) AF: 0.570 AC: 33416 AN: 58600

GnomAD4 genome AF: 0.650 AC: 98764 AN: 151946 Hom.: 34288 Cov.: 31 AF XY: 0.641 AC XY: 47607 AN XY: 74290

African (AFR) AF: 0.886 AC: 36712 AN: 41450

American (AMR) AF: 0.499 AC: 7615 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 1791 AN: 3464

East Asian (EAS) AF: 0.217 AC: 1123 AN: 5164

South Asian (SAS) AF: 0.421 AC: 2029 AN: 4814

European-Finnish (FIN) AF: 0.607 AC: 6396 AN: 10542

Middle Eastern (MID) AF: 0.521 AC: 152 AN: 292

European-Non Finnish (NFE) AF: 0.606 AC: 41192 AN: 67926

Other (OTH) AF: 0.581 AC: 1226 AN: 2110

Alfa AF: 0.622 Hom.: 16449

Bravo AF: 0.651

Asia WGS AF: 0.331 AC: 1153 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.059
DANN	Benign	0.35
PhyloP100		-0.58
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: rs7561070; hg19: chr2-11932173;