3-188484762-A-T

Variant names:

• chr3-188484762-A-T
• rs2067078
• NM_001375462.1:c.306+58A>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001375462.1(LPP):​c.306+58A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.913 in 1,295,386 control chromosomes in the GnomAD database, including 547,685 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.82 (53199 hom., cov: 30)
  • Exomes 𝑓: 0.93 (494486 hom.)
• Consequence: LPP NM_001375462.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.110
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 3-188484762-A-T is Benign according to our data. Variant chr3-188484762-A-T is described in ClinVar as [Benign]. Clinvar id is 1282245.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LPP	NM_001375462.1	c.306+58A>T		intron_variant	Intron 5 of 11	ENST00000617246.5	NP_001362391.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LPP	ENST00000617246.5	c.306+58A>T		intron_variant	Intron 5 of 11	1	NM_001375462.1	ENSP00000478901.1

Frequencies

GnomAD3 genomes AF: 0.816 AC: 124012 AN: 151892 Hom.: 53202 Cov.: 30

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.865

Gnomad AMR AF: 0.870

Gnomad ASJ AF: 0.946

Gnomad EAS AF: 0.727

Gnomad SAS AF: 0.861

Gnomad FIN AF: 0.939

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.955

Gnomad OTH AF: 0.853

GnomAD4 exome AF: 0.926 AC: 1058683 AN: 1143378 Hom.: 494486 AF XY: 0.927 AC XY: 541230 AN XY: 584106

African (AFR) AF: 0.509 AC: 13673 AN: 26850

American (AMR) AF: 0.881 AC: 38743 AN: 43992

Ashkenazi Jewish (ASJ) AF: 0.950 AC: 22789 AN: 23982

East Asian (EAS) AF: 0.692 AC: 26346 AN: 38078

South Asian (SAS) AF: 0.889 AC: 70592 AN: 79382

European-Finnish (FIN) AF: 0.941 AC: 48972 AN: 52060

Middle Eastern (MID) AF: 0.918 AC: 4721 AN: 5144

European-Non Finnish (NFE) AF: 0.956 AC: 787751 AN: 823962

Other (OTH) AF: 0.903 AC: 45096 AN: 49928

GnomAD4 genome AF: 0.816 AC: 124042 AN: 152008 Hom.: 53199 Cov.: 30 AF XY: 0.818 AC XY: 60772 AN XY: 74326

African (AFR) AF: 0.527 AC: 21795 AN: 41374

American (AMR) AF: 0.870 AC: 13292 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.946 AC: 3284 AN: 3470

East Asian (EAS) AF: 0.727 AC: 3721 AN: 5120

South Asian (SAS) AF: 0.862 AC: 4155 AN: 4818

European-Finnish (FIN) AF: 0.939 AC: 9978 AN: 10622

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.955 AC: 64971 AN: 68004

Other (OTH) AF: 0.851 AC: 1799 AN: 2114

Alfa AF: 0.880 Hom.: 7640

Bravo AF: 0.797

Asia WGS AF: 0.769 AC: 2675 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.8
DANN	Benign	0.78
PhyloP100		0.11
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: rs2067078; hg19: chr3-188202550;