rs2298711

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005570.4(LMAN1):c.1228A>T(p.Met410Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,612,408 control chromosomes in the GnomAD database, including 14,988 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1064 hom., cov: 32)

Exomes 𝑓: 0.13 ( 13924 hom. )

Consequence

LMAN1
NM_005570.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.71

Variant links:

Genes affected

LMAN1 (HGNC:6631): (lectin, mannose binding 1) The protein encoded by this gene is a membrane mannose-specific lectin that cycles between the endoplasmic reticulum, endoplasmic reticulum-Golgi intermediate compartment, and cis-Golgi, functioning as a cargo receptor for glycoprotein transport. The protein has an N-terminal signal sequence, a calcium-dependent and pH-sensitive carbohydrate recognition domain, a stalk region that functions in oligomerization, a transmembrane domain, and a short cytoplasmic domain required for organelle targeting. Allelic variants of this gene are associated with the autosomal recessive disorder combined factor V-factor VIII deficiency. [provided by RefSeq, Jul 2015]

LMAN1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014471412).

BP6

Variant 18-59333237-T-A is Benign according to our data. Variant chr18-59333237-T-A is described in ClinVar as [Benign]. Clinvar id is 259792.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMAN1	NM_005570.4 link	c.1228A>T	p.Met410Leu	missense_variant	Exon 11 of 13	ENST00000251047.6	NP_005561.1	P49257A0A024R2A7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMAN1	ENST00000251047.6 link	c.1228A>T	p.Met410Leu	missense_variant	Exon 11 of 13	1	NM_005570.4	ENSP00000251047.4		P49257
LMAN1	ENST00000587918.1 link	n.455A>T		non_coding_transcript_exon_variant	Exon 1 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.106

AC:

16131

AN:

151872

Hom.:

1065

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0292

Gnomad AMI

AF:

0.164

Gnomad AMR

AF:

0.152

Gnomad ASJ

AF:

0.107

Gnomad EAS

AF:

0.103

Gnomad SAS

AF:

0.0652

Gnomad FIN

AF:

0.122

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.142

Gnomad OTH

AF:

0.118

GnomAD3 exomes

AF:

0.121

AC:

30299

AN:

250040

Hom.:

2077

AF XY:

0.119

AC XY:

16020

AN XY:

135114

show subpopulations

Gnomad AFR exome

AF:

0.0286

Gnomad AMR exome

AF:

0.174

Gnomad ASJ exome

AF:

0.108

Gnomad EAS exome

AF:

0.100

Gnomad SAS exome

AF:

0.0646

Gnomad FIN exome

AF:

0.121

Gnomad NFE exome

AF:

0.138

Gnomad OTH exome

AF:

0.126

GnomAD4 exome

AF:

0.134

AC:

196412

AN:

1460418

Hom.:

13924

Cov.:

AF XY:

0.133

AC XY:

96280

AN XY:

726538

show subpopulations

Gnomad4 AFR exome

AF:

0.0248

Gnomad4 AMR exome

AF:

0.176

Gnomad4 ASJ exome

AF:

0.110

Gnomad4 EAS exome

AF:

0.113

Gnomad4 SAS exome

AF:

0.0659

Gnomad4 FIN exome

AF:

0.120

Gnomad4 NFE exome

AF:

0.144

Gnomad4 OTH exome

AF:

0.123

GnomAD4 genome

AF:

0.106

AC:

16136

AN:

151990

Hom.:

1064

Cov.:

AF XY:

0.106

AC XY:

7903

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.0292

Gnomad4 AMR

AF:

0.152

Gnomad4 ASJ

AF:

0.107

Gnomad4 EAS

AF:

0.103

Gnomad4 SAS

AF:

0.0655

Gnomad4 FIN

AF:

0.122

Gnomad4 NFE

AF:

0.142

Gnomad4 OTH

AF:

0.117

Alfa

AF:

0.128

Hom.:

417

Bravo

AF:

0.107

TwinsUK

AF:

0.135

AC:

501

ALSPAC

AF:

0.148

AC:

569

ESP6500AA

AF:

0.0345

AC:

152

ESP6500EA

AF:

0.135

AC:

1165

ExAC

AF:

0.118

AC:

14345

Asia WGS

AF:

0.0770

AC:

267

AN:

3472

EpiCase

AF:

0.134

EpiControl

AF:

0.131

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Factor V and factor VIII, combined deficiency of, type 1

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.61

DEOGEN2

Benign

0.081

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.71

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.65

MetaRNN

Benign

0.0014

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

PrimateAI

Benign

0.38

PROVEAN

Benign

0.090

REVEL

Benign

0.10

Sift

Benign

0.17

Sift4G

Benign

0.35

Polyphen

0.0

Vest4

0.064

MutPred

0.14

Loss of MoRF binding (P = 0.0851);

MPC

0.19

ClinPred

0.0087

GERP RS

-1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.047

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over