rs7635012

Variant names:

• chr3-188399244-C-A
• rs7635012
• NM_001375462.1:c.-9-6868C>A

Variant summary

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

The NM_001375462.1(LPP):​c.-9-6868C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 151,846 control chromosomes in the GnomAD database, including 6,136 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 0.22 (6136 hom., cov: 32)
• Consequence: LPP NM_001375462.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPP	NM_001375462.1	c.-9-6868C>A		intron_variant	Intron 3 of 11	ENST00000617246.5	NP_001362391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPP	ENST00000617246.5	c.-9-6868C>A		intron_variant	Intron 3 of 11	1	NM_001375462.1	ENSP00000478901.1

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33585 AN: 151728 Hom.: 6126 Cov.: 32

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.0901

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.0865

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.0888

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.221 AC: 33631 AN: 151846 Hom.: 6136 Cov.: 32 AF XY: 0.217 AC XY: 16112 AN XY: 74180

African (AFR) AF: 0.508 AC: 21009 AN: 41370

American (AMR) AF: 0.119 AC: 1811 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.0865 AC: 300 AN: 3468

East Asian (EAS) AF: 0.205 AC: 1057 AN: 5156

South Asian (SAS) AF: 0.0876 AC: 422 AN: 4816

European-Finnish (FIN) AF: 0.122 AC: 1284 AN: 10528

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.107 AC: 7278 AN: 67952

Other (OTH) AF: 0.175 AC: 369 AN: 2112

Alfa AF: 0.182 Hom.: 530

Bravo AF: 0.237

Asia WGS AF: 0.190 AC: 661 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.50
PhyloP100		0.049
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: rs7635012; hg19: chr3-188117032;