NM_001349206.2:c.193-47C>T

Variant names:

• chr2-11767716-C-T
• rs45509591
• NM_001349206.2:c.193-47C>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.193-47C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,253,424 control chromosomes in the GnomAD database, including 20,895 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1858 hom., cov: 32)
  • Exomes 𝑓: 0.18 (19037 hom.)
• Consequence: LPIN1 NM_001349206.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.65
• Publications: 5 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]

MIR548S (HGNC:38354): (microRNA 548s) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 2-11767716-C-T is Benign according to our data. Variant chr2-11767716-C-T is described in ClinVar as Benign. ClinVar VariationId is 262589.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPIN1	NM_001349206.2	c.193-47C>T		intron_variant	Intron 2 of 20	ENST00000674199.1	NP_001336135.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPIN1	ENST00000674199.1	c.193-47C>T		intron_variant	Intron 2 of 20		NM_001349206.2	ENSP00000501331.1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21920 AN: 151994 Hom.: 1861 Cov.: 32

Gnomad AFR AF: 0.0747

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.00347

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.146

GnomAD2 exomes AF: 0.143 AC: 35887 AN: 250136 AF XY: 0.147

Gnomad AFR exome AF: 0.0752

Gnomad AMR exome AF: 0.0732

Gnomad ASJ exome AF: 0.195

Gnomad EAS exome AF: 0.00371

Gnomad FIN exome AF: 0.172

Gnomad NFE exome AF: 0.198

Gnomad OTH exome AF: 0.158

GnomAD4 exome AF: 0.176 AC: 194206 AN: 1101312 Hom.: 19037 Cov.: 15 AF XY: 0.176 AC XY: 99497 AN XY: 565536

African (AFR) AF: 0.0721 AC: 1910 AN: 26498

American (AMR) AF: 0.0785 AC: 3471 AN: 44242

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 4636 AN: 23978

East Asian (EAS) AF: 0.00294 AC: 112 AN: 38040

South Asian (SAS) AF: 0.108 AC: 8540 AN: 79032

European-Finnish (FIN) AF: 0.166 AC: 8818 AN: 53246

Middle Eastern (MID) AF: 0.155 AC: 788 AN: 5082

European-Non Finnish (NFE) AF: 0.202 AC: 157996 AN: 782714

Other (OTH) AF: 0.164 AC: 7935 AN: 48480

GnomAD4 genome AF: 0.144 AC: 21925 AN: 152112 Hom.: 1858 Cov.: 32 AF XY: 0.141 AC XY: 10511 AN XY: 74334

African (AFR) AF: 0.0748 AC: 3106 AN: 41504

American (AMR) AF: 0.109 AC: 1672 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 677 AN: 3464

East Asian (EAS) AF: 0.00367 AC: 19 AN: 5178

South Asian (SAS) AF: 0.101 AC: 485 AN: 4816

European-Finnish (FIN) AF: 0.171 AC: 1808 AN: 10552

Middle Eastern (MID) AF: 0.202 AC: 59 AN: 292

European-Non Finnish (NFE) AF: 0.200 AC: 13620 AN: 67998

Other (OTH) AF: 0.144 AC: 303 AN: 2110

Alfa AF: 0.152 Hom.: 1501

Bravo AF: 0.136

Asia WGS AF: 0.0550 AC: 191 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 19, 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. -

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

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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	-0.96
CADD	Benign	0.030
DANN	Benign	0.42
PhyloP100		-1.6
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: rs45509591; hg19: chr2-11907842; COSMIC: COSV56765158; COSMIC: COSV56765158;