chr3-188524905-T-G

Position:

• chr3-188524905-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001375462.1(LPP):​c.429+118T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0954 in 246,186 control chromosomes in the GnomAD database, including 1,814 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1373 hom., cov: 19)
  • Exomes 𝑓: 0.076 (441 hom.)
• Consequence: LPP NM_001375462.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.342

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 3-188524905-T-G is Benign according to our data. Variant chr3-188524905-T-G is described in ClinVar as [Benign]. Clinvar id is 1224088.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LPP	NM_001375462.1	c.429+118T>G		intron_variant		ENST00000617246.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LPP	ENST00000617246.5	c.429+118T>G		intron_variant		1	NM_001375462.1	P1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 12764 AN: 105476 Hom.: 1369 Cov.: 19

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.0538

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.00255

Gnomad SAS AF: 0.0213

Gnomad FIN AF: 0.0612

Gnomad MID AF: 0.0613

Gnomad NFE AF: 0.0362

Gnomad OTH AF: 0.0951

GnomAD4 exome AF: 0.0761 AC: 10698 AN: 140638 Hom.: 441 AF XY: 0.0735 AC XY: 5331 AN XY: 72524

Gnomad4 AFR exome AF: 0.403

Gnomad4 AMR exome AF: 0.0671

Gnomad4 ASJ exome AF: 0.201

Gnomad4 EAS exome AF: 0.00502

Gnomad4 SAS exome AF: 0.0431

Gnomad4 FIN exome AF: 0.140

Gnomad4 NFE exome AF: 0.0604

Gnomad4 OTH exome AF: 0.120

GnomAD4 genome AF: 0.121 AC: 12786 AN: 105548 Hom.: 1373 Cov.: 19 AF XY: 0.122 AC XY: 6154 AN XY: 50632

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.0537

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.00256

Gnomad4 SAS AF: 0.0210

Gnomad4 FIN AF: 0.0612

Gnomad4 NFE AF: 0.0362

Gnomad4 OTH AF: 0.0941

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.5
DANN	Benign	0.30

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

Publications

LitVar

Other links and lift over

dbSNP: rs373734498; hg19: chr3-188242693;