rs2449539

Positions:

• chr8-97835027-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018407.6(LAPTM4B):​c.603+9874T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0763 in 152,278 control chromosomes in the GnomAD database, including 998 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 0.076 (998 hom., cov: 33)
• Consequence: LAPTM4B NM_018407.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.23

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAPTM4B	NM_018407.6	c.603+9874T>C		intron_variant		ENST00000521545.7	NP_060877.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAPTM4B	ENST00000521545.7	c.603+9874T>C		intron_variant		1	NM_018407.6	ENSP00000428409.1
LAPTM4B	ENST00000445593.6	c.876+9874T>C		intron_variant		1		ENSP00000402301.2
LAPTM4B	ENST00000619747.1	c.876+9874T>C		intron_variant		1		ENSP00000482533.1

Frequencies

GnomAD3 genomes AF: 0.0762 AC: 11599 AN: 152160 Hom.: 993 Cov.: 33

Gnomad AFR AF: 0.0645

Gnomad AMI AF: 0.0264

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.0528

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.0847

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.0270

Gnomad OTH AF: 0.0941

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

GnomAD4 genome AF: 0.0763 AC: 11618 AN: 152278 Hom.: 998 Cov.: 33 AF XY: 0.0855 AC XY: 6366 AN XY: 74468

Gnomad4 AFR AF: 0.0645

Gnomad4 AMR AF: 0.183

Gnomad4 ASJ AF: 0.0528

Gnomad4 EAS AF: 0.366

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.0847

Gnomad4 NFE AF: 0.0270

Gnomad4 OTH AF: 0.0964

Alfa AF: 0.0485 Hom.: 498

Bravo AF: 0.0829

Asia WGS AF: 0.271 AC: 938 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.23
DANN	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs2449539; hg19: chr8-98847255;