rs2716610

Variant names:

• chr2-11819256-C-T
• rs2716610
• NM_001349206.2:c.2403-228C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-11819256-C-T
• chr2-11819256-C-G

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.2403-228C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 532,774 control chromosomes in the GnomAD database, including 14,232 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (7749 hom., cov: 32)
  • Exomes 𝑓: 0.17 (6483 hom.)
• Consequence: LPIN1 NM_001349206.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.297
• Publications: 7 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, Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine
• 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=-0.84).
• BP6: Variant 2-11819256-C-T is Benign according to our data. Variant chr2-11819256-C-T is described in ClinVar as Benign. ClinVar VariationId is 1295169.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349206.2. 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
	LPIN1	NM_001349206.2	MANE Select	c.2403-228C>T		intron	N/A	NP_001336135.1	Q14693-3
	LPIN1	NM_001261428.3		c.2550-228C>T		intron	N/A	NP_001248357.1	Q14693-7
	LPIN1	NM_001349207.2		c.2493-228C>T		intron	N/A	NP_001336136.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPIN1	ENST00000674199.1	MANE Select	c.2403-228C>T		intron	N/A	ENSP00000501331.1	Q14693-3
	LPIN1	ENST00000256720.6	TSL:1	c.2295-228C>T		intron	N/A	ENSP00000256720.2	Q14693-1
	LPIN1	ENST00000404113.6	TSL:1	n.1888-228C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40066 AN: 151796 Hom.: 7703 Cov.: 32

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.0918

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.242

GnomAD4 exome AF: 0.166 AC: 63077 AN: 380860 Hom.: 6483 Cov.: 0 AF XY: 0.163 AC XY: 33105 AN XY: 203068

African (AFR) AF: 0.540 AC: 5786 AN: 10720

American (AMR) AF: 0.203 AC: 3055 AN: 15014

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 3157 AN: 11514

East Asian (EAS) AF: 0.116 AC: 2955 AN: 25420

South Asian (SAS) AF: 0.148 AC: 6202 AN: 41964

European-Finnish (FIN) AF: 0.0940 AC: 2109 AN: 22426

Middle Eastern (MID) AF: 0.289 AC: 468 AN: 1622

European-Non Finnish (NFE) AF: 0.152 AC: 35020 AN: 230304

Other (OTH) AF: 0.198 AC: 4325 AN: 21876

GnomAD4 genome AF: 0.264 AC: 40165 AN: 151914 Hom.: 7749 Cov.: 32 AF XY: 0.259 AC XY: 19260 AN XY: 74234

African (AFR) AF: 0.537 AC: 22255 AN: 41414

American (AMR) AF: 0.209 AC: 3190 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 1034 AN: 3464

East Asian (EAS) AF: 0.146 AC: 754 AN: 5160

South Asian (SAS) AF: 0.148 AC: 711 AN: 4810

European-Finnish (FIN) AF: 0.0918 AC: 968 AN: 10546

Middle Eastern (MID) AF: 0.346 AC: 101 AN: 292

European-Non Finnish (NFE) AF: 0.155 AC: 10528 AN: 67954

Other (OTH) AF: 0.238 AC: 503 AN: 2110

Alfa AF: 0.156 Hom.: 835

Bravo AF: 0.289

Asia WGS AF: 0.150 AC: 523 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.91
DANN	Benign	0.62
PhyloP100		-0.30
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: rs2716610; hg19: chr2-11959382;