8-97775784-C-T

Variant names:

• chr8-97775784-C-T
• rs114241480
• ENST00000445593.6:c.48C>T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The ENST00000445593.6(LAPTM4B):​c.48C>T​(p.Leu16Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00307 in 1,552,084 control chromosomes in the GnomAD database, including 145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (79 hom., cov: 31)
  • Exomes 𝑓: 0.0016 (66 hom.)
• Consequence: LAPTM4B ENST00000445593.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.281

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

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 8-97775784-C-T is Benign according to our data. Variant chr8-97775784-C-T is described in ClinVar as [Benign]. Clinvar id is 775266.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.281 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAPTM4B	NM_018407.6	c.-226C>T		upstream_gene_variant		ENST00000521545.7	NP_060877.4
LOC124901986	XR_007061020.1	n.-9G>A		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAPTM4B	ENST00000445593.6	c.48C>T	p.Leu16Leu	synonymous_variant	Exon 1 of 7	1		ENSP00000402301.2
LAPTM4B	ENST00000619747.1	c.48C>T	p.Leu16Leu	synonymous_variant	Exon 1 of 7	1		ENSP00000482533.1
LAPTM4B	ENST00000521545.7	c.-226C>T		upstream_gene_variant		1	NM_018407.6	ENSP00000428409.1
LAPTM4B	ENST00000517924.5	c.-226C>T		upstream_gene_variant		5		ENSP00000429868.2

Frequencies

GnomAD3 genomes AF: 0.0166 AC: 2458 AN: 147672 Hom.: 79 Cov.: 31

Gnomad AFR AF: 0.0557

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00801

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000170

Gnomad OTH AF: 0.0161

GnomAD3 exomes AF: 0.00372 AC: 645 AN: 173534 Hom.: 12 AF XY: 0.00268 AC XY: 259 AN XY: 96764

Gnomad AFR exome AF: 0.0579

Gnomad AMR exome AF: 0.00312

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000751

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000818

Gnomad OTH exome AF: 0.00170

GnomAD4 exome AF: 0.00164 AC: 2309 AN: 1404302 Hom.: 66 Cov.: 40 AF XY: 0.00143 AC XY: 996 AN XY: 696540

Gnomad4 AFR exome AF: 0.0574

Gnomad4 AMR exome AF: 0.00333

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000108

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000709

Gnomad4 OTH exome AF: 0.00361

GnomAD4 genome AF: 0.0167 AC: 2462 AN: 147782 Hom.: 79 Cov.: 31 AF XY: 0.0165 AC XY: 1197 AN XY: 72406

Gnomad4 AFR AF: 0.0557

Gnomad4 AMR AF: 0.00800

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000170

Gnomad4 OTH AF: 0.0160

Alfa AF: 0.000968 Hom.: 0

Bravo AF: 0.0185

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 19, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	3.5
DANN	Benign	0.94

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: rs114241480; hg19: chr8-98788012;