13-113309838-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005561.4(LAMP1):c.379C>G(p.Leu127Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00151 in 1,613,162 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0022 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 60 hom. )

Consequence

LAMP1
NM_005561.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.83

Publications

2 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013619006).

BP6

Variant 13-113309838-C-G is Benign according to our data. Variant chr13-113309838-C-G is described in ClinVar as [Benign]. Clinvar id is 791368.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00219 (334/152340) while in subpopulation AMR AF = 0.0198 (303/15298). AF 95% confidence interval is 0.018. There are 8 homozygotes in GnomAd4. There are 173 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMP1	NM_005561.4 link	c.379C>G	p.Leu127Val	missense_variant	Exon 3 of 9	ENST00000332556.5	NP_005552.3	P11279-1A0A024RDY3
LAMP1	XM_011537494.3 link	c.322C>G	p.Leu108Val	missense_variant	Exon 3 of 9		XP_011535796.1
LAMP1	XM_047430302.1 link	c.313C>G	p.Leu105Val	missense_variant	Exon 3 of 9		XP_047286258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMP1	ENST00000332556.5 link	c.379C>G	p.Leu127Val	missense_variant	Exon 3 of 9	1	NM_005561.4	ENSP00000333298.4		P11279-1
LAMP1	ENST00000472564.1 link	n.1871C>G		non_coding_transcript_exon_variant	Exon 2 of 6	2

Frequencies

GnomAD3 genomes

AF:

0.00219

AC:

333

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0198

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00641

AC:

1599

AN:

249442

AF XY:

0.00503

show subpopulations

Gnomad AFR exome

AF:

0.000194

Gnomad AMR exome

AF:

0.0453

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000106

Gnomad OTH exome

AF:

0.00347

GnomAD4 exome

AF:

0.00144

AC:

2099

AN:

1460822

Hom.:

Cov.:

AF XY:

0.00129

AC XY:

941

AN XY:

726740

show subpopulations

African (AFR)

AF:

0.000209

AC:

AN:

33452

American (AMR)

AF:

0.0434

AC:

1942

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000928

AC:

AN:

86194

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4998

European-Non Finnish (NFE)

AF:

0.0000540

AC:

AN:

1111922

Other (OTH)

AF:

0.00133

AC:

AN:

60294

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

198

296

395

494

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00219

AC:

334

AN:

152340

Hom.:

Cov.:

AF XY:

0.00232

AC XY:

173

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.000361

AC:

AN:

41580

American (AMR)

AF:

0.0198

AC:

303

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68032

Other (OTH)

AF:

0.00236

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000617

Hom.:

Bravo

AF:

0.00437

ESP6500AA

AF:

0.000262

AC:

ESP6500EA

AF:

0.000242

AC:

ExAC

AF:

0.00468

AC:

565

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 31, 2019

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

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.014

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.095

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.46

MetaRNN

Benign

0.014

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.83

PhyloP100

-1.8

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.32

REVEL

Benign

0.0

Sift

Benign

0.62

Sift4G

Benign

0.28

Polyphen

0.0080

Vest4

0.089

MVP

0.17

MPC

0.28

ClinPred

0.0019

GERP RS

-8.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.020

gMVP

0.25

Mutation Taster

=92/8

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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13-113309838-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over