13-113309838-C-G

Variant names:

• chr13-113309838-C-G
• rs111455645
• NM_005561.4:c.379C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.83
• Publications: 2 publications found

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]

ACMG classification

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 VariationId 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005561.4. 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
	LAMP1	NM_005561.4	MANE Select	c.379C>G	p.Leu127Val	missense	Exon 3 of 9	NP_005552.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMP1	ENST00000332556.5	TSL:1 MANE Select	c.379C>G	p.Leu127Val	missense	Exon 3 of 9	ENSP00000333298.4	P11279-1
	LAMP1	ENST00000886119.1		c.379C>G	p.Leu127Val	missense	Exon 3 of 10	ENSP00000556178.1
	LAMP1	ENST00000886115.1		c.379C>G	p.Leu127Val	missense	Exon 3 of 9	ENSP00000556174.1

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

GnomAD2 exomes AF: 0.00641 AC: 1599 AN: 249442 AF XY: 0.00503

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

African (AFR) AF: 0.000209 AC: 7 AN: 33452

American (AMR) AF: 0.0434 AC: 1942 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.0000928 AC: 8 AN: 86194

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4998

European-Non Finnish (NFE) AF: 0.0000540 AC: 60 AN: 1111922

Other (OTH) AF: 0.00133 AC: 80 AN: 60294

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

African (AFR) AF: 0.000361 AC: 15 AN: 41580

American (AMR) AF: 0.0198 AC: 303 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68032

Other (OTH) AF: 0.00236 AC: 5 AN: 2116

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		-1.8
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
Mutation Taster		=92/8	polymorphism (auto)

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

Other links and lift over

dbSNP: rs111455645; hg19: chr13-113964153;