18-2990702-A-G

Variant names:

• chr18-2990702-A-G
• rs661767
• NM_001375808.2:c.-10+22385T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001375808.2(LPIN2):​c.-10+22385T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 306,672 control chromosomes in the GnomAD database, including 73,297 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.65 (33419 hom., cov: 34)
  • Exomes 𝑓: 0.71 (39878 hom.)
• Consequence: LPIN2 NM_001375808.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.228
• Publications: 9 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]

SNRPCP4 (HGNC:49819): (small nuclear ribonucleoprotein polypeptide C pseudogene 4)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.819 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPIN2	NM_001375808.2	MANE Select	c.-10+22385T>C		intron	N/A	NP_001362737.1
	LPIN2	NM_001375809.1		c.-10+22335T>C		intron	N/A	NP_001362738.1
	LPIN2	NM_014646.2		c.-10+21016T>C		intron	N/A	NP_055461.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LPIN2	ENST00000677752.1	MANE Select	c.-10+22385T>C		intron	N/A	ENSP00000504857.1
	LPIN2	ENST00000261596.9	TSL:1	c.-10+21016T>C		intron	N/A	ENSP00000261596.4
	SNRPCP4	ENST00000583992.1	TSL:6	n.51A>G		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.645 AC: 98137 AN: 152042 Hom.: 33402 Cov.: 34

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.641

Gnomad AMR AF: 0.722

Gnomad ASJ AF: 0.743

Gnomad EAS AF: 0.840

Gnomad SAS AF: 0.654

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.729

Gnomad OTH AF: 0.663

GnomAD4 exome AF: 0.713 AC: 110104 AN: 154514 Hom.: 39878 Cov.: 0 AF XY: 0.707 AC XY: 59247 AN XY: 83832

African (AFR) AF: 0.406 AC: 1872 AN: 4606

American (AMR) AF: 0.758 AC: 7080 AN: 9346

Ashkenazi Jewish (ASJ) AF: 0.734 AC: 2592 AN: 3530

East Asian (EAS) AF: 0.860 AC: 6191 AN: 7196

South Asian (SAS) AF: 0.644 AC: 19071 AN: 29592

European-Finnish (FIN) AF: 0.772 AC: 5440 AN: 7046

Middle Eastern (MID) AF: 0.641 AC: 345 AN: 538

European-Non Finnish (NFE) AF: 0.730 AC: 62032 AN: 84954

Other (OTH) AF: 0.711 AC: 5481 AN: 7706

GnomAD4 genome AF: 0.645 AC: 98192 AN: 152158 Hom.: 33419 Cov.: 34 AF XY: 0.649 AC XY: 48276 AN XY: 74386

African (AFR) AF: 0.412 AC: 17108 AN: 41502

American (AMR) AF: 0.722 AC: 11041 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.743 AC: 2578 AN: 3470

East Asian (EAS) AF: 0.840 AC: 4349 AN: 5176

South Asian (SAS) AF: 0.653 AC: 3153 AN: 4828

European-Finnish (FIN) AF: 0.779 AC: 8238 AN: 10576

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.729 AC: 49542 AN: 68000

Other (OTH) AF: 0.664 AC: 1404 AN: 2116

Alfa AF: 0.704 Hom.: 55156

Bravo AF: 0.638

Asia WGS AF: 0.691 AC: 2405 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	2.9
DANN	Benign	0.59
PhyloP100		-0.23
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: rs661767; hg19: chr18-2990700;