Genetic Variant LAMP1:p.Ala204Val (chr13-113319517-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_005561.4(LAMP1):c.611C>T(p.Ala204Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0151 in 1,613,710 control chromosomes in the GnomAD database, including 1,626 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.054 ( 613 hom., cov: 33)

Exomes 𝑓: 0.011 ( 1013 hom. )

Consequence

LAMP1
NM_005561.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.625

Publications

14 publications found

Variant links:

Genes affected

LAMP1 (HGNC:6499): (lysosomal associated membrane protein 1) The protein encoded by this gene is a member of a family of membrane glycoproteins. This glycoprotein provides selectins with carbohydrate ligands. It may also play a role in tumor cell metastasis. [provided by RefSeq, Jul 2008]

LAMP1 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 (MetaRNN=0.0015163422).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMP1	NM_005561.4 link	c.611C>T	p.Ala204Val	missense_variant	Exon 5 of 9	ENST00000332556.5	NP_005552.3	P11279-1A0A024RDY3
LAMP1	XM_011537494.3 link	c.554C>T	p.Ala185Val	missense_variant	Exon 5 of 9		XP_011535796.1
LAMP1	XM_047430302.1 link	c.545C>T	p.Ala182Val	missense_variant	Exon 5 of 9		XP_047286258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMP1	ENST00000332556.5 link	c.611C>T	p.Ala204Val	missense_variant	Exon 5 of 9	1	NM_005561.4	ENSP00000333298.4		P11279-1
LAMP1	ENST00000472564.1 link	n.2103C>T		non_coding_transcript_exon_variant	Exon 4 of 6	2

Frequencies

GnomAD3 genomes

AF:

0.0540

AC:

8222

AN:

152170

Hom.:

612

Cov.:

show subpopulations

Gnomad AFR

AF:

0.158

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.139

Gnomad SAS

AF:

0.00641

Gnomad FIN

AF:

0.00772

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000794

Gnomad OTH

AF:

0.0392

GnomAD2 exomes

AF:

0.0314

AC:

7766

AN:

247380

AF XY:

0.0261

show subpopulations

Gnomad AFR exome

AF:

0.161

Gnomad AMR exome

AF:

0.0610

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.153

Gnomad FIN exome

AF:

0.00776

Gnomad NFE exome

AF:

0.000699

Gnomad OTH exome

AF:

0.0153

GnomAD4 exome

AF:

0.0110

AC:

16086

AN:

1461422

Hom.:

1013

Cov.:

AF XY:

0.0100

AC XY:

7297

AN XY:

727022

show subpopulations

African (AFR)

AF:

0.168

AC:

5610

AN:

33478

American (AMR)

AF:

0.0583

AC:

2605

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.136

AC:

5397

AN:

39696

South Asian (SAS)

AF:

0.00328

AC:

283

AN:

86210

European-Finnish (FIN)

AF:

0.00613

AC:

326

AN:

53166

Middle Eastern (MID)

AF:

0.00850

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000512

AC:

569

AN:

1111888

Other (OTH)

AF:

0.0206

AC:

1247

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

746

1491

2237

2982

3728

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

308

616

924

1232

1540

<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:

0.0542

AC:

8251

AN:

152288

Hom.:

613

Cov.:

AF XY:

0.0541

AC XY:

4029

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.158

AC:

6574

AN:

41532

American (AMR)

AF:

0.0461

AC:

706

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.139

AC:

720

AN:

5174

South Asian (SAS)

AF:

0.00641

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00772

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000794

AC:

AN:

68028

Other (OTH)

AF:

0.0393

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

351

702

1053

1404

1755

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

246

328

410

<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:

0.0219

Hom.:

457

Bravo

AF:

0.0634

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.154

AC:

623

ESP6500EA

AF:

0.000835

AC:

ExAC

AF:

0.0308

AC:

3730

Asia WGS

AF:

0.0530

AC:

186

AN:

3478

EpiCase

AF:

0.000873

EpiControl

AF:

0.000771

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.86

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.082

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.48

MetaRNN

Benign

0.0015

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.59

PhyloP100

-0.63

PrimateAI

Benign

0.28

PROVEAN

Benign

0.13

REVEL

Benign

0.014

Sift

Benign

0.30

Sift4G

Benign

0.30

Polyphen

0.017

Vest4

0.038

MPC

0.27

ClinPred

0.0056

GERP RS

0.16

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.026

gMVP

0.34

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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