rs764278197

Positions:

• chr8-97775937-C-CGGCGGGCTCCAGGCGA
• chr8-97775937-C-CGGCGGGCTCCAGGCGAGGCGGGCTCCAGGCGA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000445593.6(LAPTM4B):​c.207_222dup​(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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0660

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]

ACMG classification

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/exons	MANE	UniProt
LAPTM4B	NM_018407.6	c.-67_-52dup		5_prime_UTR_variant	1/7	ENST00000521545.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAPTM4B	ENST00000445593.6	c.207_222dup	p.Ser75AlafsTer71	frameshift_variant	1/7	1
LAPTM4B	ENST00000619747.1	c.207_222dup	p.Ser75AlafsTer71	frameshift_variant	1/7	1
LAPTM4B	ENST00000521545.7	c.-67_-52dup		5_prime_UTR_variant	1/7	1	NM_018407.6	P1
LAPTM4B	ENST00000517924.5	c.-67_-52dup		5_prime_UTR_variant	1/5	5

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

GnomAD3 exomes AF: 0.0649 AC: 4110 AN: 63330 Hom.: 267 AF XY: 0.0652 AC XY: 2382 AN XY: 36534

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

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.: 31 AF XY: 0.113 AC XY: 8380 AN XY: 74238

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.: 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

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs764278197; hg19: chr8-98788165;