Genetic Variant LAPTM4B:c.211+132T>C (chr8-97805596-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.140

Publications

0 publications found

Variant links:

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]

LAPTM4B links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018407.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAPTM4B	NM_018407.6	MANE Select	c.211+132T>C		intron	N/A	NP_060877.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LAPTM4B	ENST00000521545.7	TSL:1 MANE Select	c.211+132T>C	intron	N/A	ENSP00000428409.1	Q86VI4-2
LAPTM4B	ENST00000445593.6	TSL:1	c.484+132T>C	intron	N/A	ENSP00000402301.2	Q86VI4-3
LAPTM4B	ENST00000619747.1	TSL:1	c.484+132T>C	intron	N/A	ENSP00000482533.1	Q86VI4-3

Frequencies

GnomAD3 genomes

AF:

0.0612

AC:

9307

AN:

152110

Hom.:

826

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.191

AC:

2543

AN:

13346

American (AMR)

AF:

0.0241

AC:

561

AN:

23276

Ashkenazi Jewish (ASJ)

AF:

0.0237

AC:

358

AN:

15090

East Asian (EAS)

AF:

0.0000307

AC:

AN:

32554

South Asian (SAS)

AF:

0.00585

AC:

289

AN:

49438

European-Finnish (FIN)

AF:

0.000354

AC:

AN:

36756

Middle Eastern (MID)

AF:

0.0855

AC:

299

AN:

3496

European-Non Finnish (NFE)

AF:

0.00546

AC:

1588

AN:

290724

Other (OTH)

AF:

0.0259

AC:

716

AN:

27696

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

254

508

761

1015

1269

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

162

216

270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0613

AC:

9324

AN:

152228

Hom.:

826

Cov.:

AF XY:

0.0597

AC XY:

4447

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.193

AC:

8013

AN:

41502

American (AMR)

AF:

0.0439

AC:

671

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0248

AC:

AN:

3470

East Asian (EAS)

AF:

0.000578

AC:

AN:

5190

South Asian (SAS)

AF:

0.00684

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.000565

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.106

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00534

AC:

363

AN:

68026

Other (OTH)

AF:

0.0558

AC:

118

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

371

741

1112

1482

1853

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

258

344

430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0413

Hom.:

Bravo

AF:

0.0707

Asia WGS

AF:

0.0140

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.1

(source)

DANN

Benign

0.31

PhyloP100

-0.14

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over