chr3-188759802-A-G

Variant names:

• chr3-188759802-A-G
• rs3817462
• NM_001375462.1:c.1241-311A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001375462.1(LPP):​c.1241-311A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,150 control chromosomes in the GnomAD database, including 956 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.10 (956 hom., cov: 32)
• Consequence: LPP NM_001375462.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.304
• Publications: 4 publications found

Genes affected

LPP (HGNC:6679): (LIM domain containing preferred translocation partner in lipoma) This gene encodes a member of a subfamily of LIM domain proteins that are characterized by an N-terminal proline-rich region and three C-terminal LIM domains. The encoded protein localizes to the cell periphery in focal adhesions and may be involved in cell-cell adhesion and cell motility. This protein also shuttles through the nucleus and may function as a transcriptional co-activator. This gene is located at the junction of certain disease-related chromosomal translocations, which result in the expression of chimeric proteins that may promote tumor growth. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 3-188759802-A-G is Benign according to our data. Variant chr3-188759802-A-G is described in ClinVar as Benign. ClinVar VariationId is 1265876.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPP	NM_001375462.1	c.1241-311A>G		intron_variant	Intron 8 of 11	ENST00000617246.5	NP_001362391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPP	ENST00000617246.5	c.1241-311A>G		intron_variant	Intron 8 of 11	1	NM_001375462.1	ENSP00000478901.1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15473 AN: 152032 Hom.: 951 Cov.: 32

Gnomad AFR AF: 0.0521

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.0751

Gnomad ASJ AF: 0.0867

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.116

Gnomad OTH AF: 0.0929

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.102 AC: 15487 AN: 152150 Hom.: 956 Cov.: 32 AF XY: 0.105 AC XY: 7831 AN XY: 74374

African (AFR) AF: 0.0521 AC: 2164 AN: 41536

American (AMR) AF: 0.0752 AC: 1150 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0867 AC: 301 AN: 3470

East Asian (EAS) AF: 0.155 AC: 801 AN: 5162

South Asian (SAS) AF: 0.206 AC: 987 AN: 4802

European-Finnish (FIN) AF: 0.170 AC: 1801 AN: 10588

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.116 AC: 7885 AN: 67992

Other (OTH) AF: 0.0924 AC: 195 AN: 2110

Alfa AF: 0.108 Hom.: 2019

Bravo AF: 0.0912

Asia WGS AF: 0.168 AC: 583 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.9
DANN	Benign	0.64
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3817462; hg19: chr3-188477590;