Variant 8-97775937-C-CGGCGGGCTCCAGGCGA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The ENST00000445593.6(LAPTM4B):c.207_222dupGCTCCAGGCGAGGCGG(p.Ser75AlafsTer71) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,449,128 control chromosomes in the GnomAD database, including 14,898 homozygotes. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.12 ( 1178 hom., cov: 31)

Exomes 𝑓: 0.14 ( 13720 hom. )

Consequence

LAPTM4B
ENST00000445593.6 frameshift

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0660

Variant links:

Genes affected

LAPTM4B (HGNC:13646): (lysosomal protein transmembrane 4 beta) Enables ceramide binding activity; enzyme binding activity; and phosphatidylinositol bisphosphate binding activity. Involved in several processes, including negative regulation of macromolecule metabolic process; regulation of lysosomal membrane permeability; and regulation of lysosome organization. Located in several cellular components, including endosome; lysosomal membrane; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

LAPTM4B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 8-97775937-C-CGGCGGGCTCCAGGCGA is Benign according to our data. Variant chr8-97775937-C-CGGCGGGCTCCAGGCGA is described in ClinVar as [Benign]. Clinvar id is 403028.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAPTM4B	NM_018407.6 link	c.-67_-52dupGCTCCAGGCGAGGCGG		5_prime_UTR_variant	Exon 1 of 7	ENST00000521545.7	NP_060877.4	Q86VI4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LAPTM4B	ENST00000445593.6 link	c.207_222dupGCTCCAGGCGAGGCGG	p.Ser75AlafsTer71	frameshift_variant	Exon 1 of 7	1		ENSP00000402301.2	Q86VI4-3
LAPTM4B	ENST00000619747.1 link	c.207_222dupGCTCCAGGCGAGGCGG	p.Ser75AlafsTer71	frameshift_variant	Exon 1 of 7	1		ENSP00000482533.1	Q86VI4-3
LAPTM4B	ENST00000521545 link	c.-67_-52dupGCTCCAGGCGAGGCGG		5_prime_UTR_variant	Exon 1 of 7	1	NM_018407.6	ENSP00000428409.1	Q86VI4-2
LAPTM4B	ENST00000517924 link	c.-67_-52dupGCTCCAGGCGAGGCGG		5_prime_UTR_variant	Exon 1 of 5	5		ENSP00000429868.2	H0YBN1

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17567

AN:

151766

Hom.:

1178

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0607

Gnomad AMI

AF:

0.126

Gnomad AMR

AF:

0.0930

Gnomad ASJ

AF:

0.229

Gnomad EAS

AF:

0.00136

Gnomad SAS

AF:

0.134

Gnomad FIN

AF:

0.109

Gnomad MID

AF:

0.248

Gnomad NFE

AF:

0.156

Gnomad OTH

AF:

0.134

GnomAD3 exomes

AF:

0.0649

AC:

4110

AN:

63330

Hom.:

267

AF XY:

0.0652

AC XY:

2382

AN XY:

36534

show subpopulations

Gnomad AFR exome

AF:

0.0209

Gnomad AMR exome

AF:

0.0434

Gnomad ASJ exome

AF:

0.161

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0772

Gnomad FIN exome

AF:

0.0524

Gnomad NFE exome

AF:

0.0680

Gnomad OTH exome

AF:

0.0841

GnomAD4 exome

AF:

0.142

AC:

184513

AN:

1297252

Hom.:

13720

Cov.:

AF XY:

0.142

AC XY:

90428

AN XY:

637568

show subpopulations

Gnomad4 AFR exome

AF:

0.0579

Gnomad4 AMR exome

AF:

0.0692

Gnomad4 ASJ exome

AF:

0.221

Gnomad4 EAS exome

AF:

0.000313

Gnomad4 SAS exome

AF:

0.128

Gnomad4 FIN exome

AF:

0.103

Gnomad4 NFE exome

AF:

0.151

Gnomad4 OTH exome

AF:

0.141

GnomAD4 genome

AF:

0.116

AC:

17567

AN:

151876

Hom.:

1178

Cov.:

AF XY:

0.113

AC XY:

8380

AN XY:

74238

show subpopulations

Gnomad4 AFR

AF:

0.0606

Gnomad4 AMR

AF:

0.0928

Gnomad4 ASJ

AF:

0.229

Gnomad4 EAS

AF:

0.00136

Gnomad4 SAS

AF:

0.134

Gnomad4 FIN

AF:

0.109

Gnomad4 NFE

AF:

0.156

Gnomad4 OTH

AF:

0.133

Alfa

AF:

0.0467

Hom.:

Asia WGS

AF:

0.0610

AC:

215

AN:

3452

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Not present in FAST (frequency). ExAC: 23.9% (9166/38406) total chromosomes -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over