13-113309838-C-G

Position:

• chr13-113309838-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000332556.5(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. 14/20 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 ENST00000332556.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.83

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMP1	NM_005561.4	c.379C>G	p.Leu127Val	missense_variant	3/9	ENST00000332556.5	NP_005552.3
LAMP1	XM_011537494.3	c.322C>G	p.Leu108Val	missense_variant	3/9		XP_011535796.1
LAMP1	XM_047430302.1	c.313C>G	p.Leu105Val	missense_variant	3/9		XP_047286258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAMP1	ENST00000332556.5	c.379C>G	p.Leu127Val	missense_variant	3/9	1	NM_005561.4	ENSP00000333298.4
LAMP1	ENST00000472564.1	n.1871C>G		non_coding_transcript_exon_variant	2/6	2

Frequencies

GnomAD3 genomes AF: 0.00219 AC: 333 AN: 152222 Hom.: 8 Cov.: 32

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

GnomAD3 exomes AF: 0.00641 AC: 1599 AN: 249442 Hom.: 48 AF XY: 0.00503 AC XY: 681 AN XY: 135342

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 SAS exome AF: 0.0000654

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.: 60 Cov.: 31 AF XY: 0.00129 AC XY: 941 AN XY: 726740

Gnomad4 AFR exome AF: 0.000209

Gnomad4 AMR exome AF: 0.0434

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.0000928

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000540

Gnomad4 OTH exome AF: 0.00133

GnomAD4 genome AF: 0.00219 AC: 334 AN: 152340 Hom.: 8 Cov.: 32 AF XY: 0.00232 AC XY: 173 AN XY: 74486

Gnomad4 AFR AF: 0.000361

Gnomad4 AMR AF: 0.0198

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.000617 Hom.: 1

Bravo AF: 0.00437

ESP6500AA AF: 0.000262 AC: 1

ESP6500EA AF: 0.000242 AC: 2

ExAC AF: 0.00468 AC: 565

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.014
DANN	Benign	0.65
DEOGEN2	Benign	0.095	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.46	T
MetaRNN	Benign	0.014	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.83	L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.32	N
REVEL	Benign	0.0
Sift	Benign	0.62	T
Sift4G	Benign	0.28	T
Polyphen		0.0080	B
Vest4		0.089
MVP		0.17
MPC		0.28
ClinPred		0.0019	T
GERP RS		-8.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.020
gMVP		0.25

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: rs111455645; hg19: chr13-113964153;