ENST00000445593.6:c.207_222dupGCTCCAGGCGAGGCGG

Variant names:

• chr8-97775937-C-CGGCGGGCTCCAGGCGA
• rs764278197
• ENST00000445593.6:c.207_222dupGCTCCAGGCGAGGCGG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

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. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0660
• Publications: 0 publications found

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]

LOC124901986 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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	c.-67_-52dupGCTCCAGGCGAGGCGG		5_prime_UTR_variant	Exon 1 of 7	ENST00000521545.7	NP_060877.4
LOC124901986	XR_007061020.1	n.-178_-163dupTCGCCTGGAGCCCGCC		upstream_gene_variant

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17567 AN: 151766 Hom.: 1178 Cov.: 31

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

GnomAD2 exomes AF: 0.0649 AC: 4110 AN: 63330 AF XY: 0.0652

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 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.: 35 AF XY: 0.142 AC XY: 90428 AN XY: 637568

African (AFR) AF: 0.0579 AC: 1538 AN: 26554

American (AMR) AF: 0.0692 AC: 1505 AN: 21756

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 4561 AN: 20594

East Asian (EAS) AF: 0.000313 AC: 9 AN: 28796

South Asian (SAS) AF: 0.128 AC: 8403 AN: 65454

European-Finnish (FIN) AF: 0.103 AC: 3830 AN: 37310

Middle Eastern (MID) AF: 0.171 AC: 666 AN: 3894

European-Non Finnish (NFE) AF: 0.151 AC: 156446 AN: 1039212

Other (OTH) AF: 0.141 AC: 7555 AN: 53682

GnomAD4 genome AF: 0.116 AC: 17567 AN: 151876 Hom.: 1178 Cov.: 31 AF XY: 0.113 AC XY: 8380 AN XY: 74238

African (AFR) AF: 0.0606 AC: 2517 AN: 41530

American (AMR) AF: 0.0928 AC: 1418 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 794 AN: 3462

East Asian (EAS) AF: 0.00136 AC: 7 AN: 5148

South Asian (SAS) AF: 0.134 AC: 648 AN: 4824

European-Finnish (FIN) AF: 0.109 AC: 1152 AN: 10542

Middle Eastern (MID) AF: 0.243 AC: 70 AN: 288

European-Non Finnish (NFE) AF: 0.156 AC: 10567 AN: 67794

Other (OTH) AF: 0.133 AC: 280 AN: 2108

Alfa AF: 0.0467 Hom.: 52

Asia WGS AF: 0.0610 AC: 215 AN: 3452

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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
PhyloP100		0.066
Mutation Taster		=164/36	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs764278197; hg19: chr8-98788165; COSMIC: COSV63392838; COSMIC: COSV63392838;