dbSNP rs10504978: 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:

Genome browser will be placed here

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAPTM4B	NM_018407.6 link	c.211+132T>C		intron_variant	Intron 2 of 6	ENST00000521545.7	NP_060877.4	Q86VI4-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
LAPTM4B	ENST00000521545.7 link	c.211+132T>C	intron_variant	Intron 2 of 6	1	NM_018407.6	ENSP00000428409.1	Q86VI4-2
LAPTM4B	ENST00000445593.6 link	c.484+132T>C	intron_variant	Intron 2 of 6	1		ENSP00000402301.2	Q86VI4-3
LAPTM4B	ENST00000619747.1 link	c.484+132T>C	intron_variant	Intron 2 of 6	1		ENSP00000482533.1	Q86VI4-3
LAPTM4B	ENST00000517924.5 link	c.211+132T>C	intron_variant	Intron 2 of 4	5		ENSP00000429868.2	H0YBN1

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over