rs10504978

Positions:

• chr8-97805596-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.211+132T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0243 in 644,604 control chromosomes in the GnomAD database, including 1,133 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 0.061 (826 hom., cov: 31)
  • Exomes 𝑓: 0.013 (307 hom.)
• Consequence: LAPTM4B NM_018407.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.140

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAPTM4B	NM_018407.6	c.211+132T>C		intron_variant		ENST00000521545.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAPTM4B	ENST00000521545.7	c.211+132T>C		intron_variant		1	NM_018407.6	P1
LAPTM4B	ENST00000445593.6	c.484+132T>C		intron_variant		1
LAPTM4B	ENST00000619747.1	c.484+132T>C		intron_variant		1
LAPTM4B	ENST00000517924.5	c.211+132T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0612 AC: 9307 AN: 152110 Hom.: 826 Cov.: 31

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0440

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.00705

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.00534

Gnomad OTH AF: 0.0564

GnomAD4 exome AF: 0.0129 AC: 6368 AN: 492376 Hom.: 307 AF XY: 0.0121 AC XY: 3199 AN XY: 263514

Gnomad4 AFR exome AF: 0.191

Gnomad4 AMR exome AF: 0.0241

Gnomad4 ASJ exome AF: 0.0237

Gnomad4 EAS exome AF: 0.0000307

Gnomad4 SAS exome AF: 0.00585

Gnomad4 FIN exome AF: 0.000354

Gnomad4 NFE exome AF: 0.00546

Gnomad4 OTH exome AF: 0.0259

GnomAD4 genome AF: 0.0613 AC: 9324 AN: 152228 Hom.: 826 Cov.: 31 AF XY: 0.0597 AC XY: 4447 AN XY: 74438

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.0439

Gnomad4 ASJ AF: 0.0248

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.00684

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.00534

Gnomad4 OTH AF: 0.0558

Alfa AF: 0.0371 Hom.: 62

Bravo AF: 0.0707

Asia WGS AF: 0.0140 AC: 47 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.31
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs10504978; hg19: chr8-98817824;