rs33926449

Positions:

chr18-59359129-A-G

Variant summary

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

The NM_005570.4(LMAN1):c.116T>C(p.Val39Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0835 in 1,613,990 control chromosomes in the GnomAD database, including 6,154 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 0.093 ( 797 hom., cov: 32)

Exomes 𝑓: 0.082 ( 5357 hom. )

Consequence

LMAN1
NM_005570.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.253

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:

LMAN1 (HGNC:):

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=0.0016942322).

BP6

Variant 18-59359129-A-G is Benign according to our data. Variant chr18-59359129-A-G is described in ClinVar as [Benign]. Clinvar id is 259791.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMAN1	NM_005570.4 linkuse as main transcript	c.116T>C	p.Val39Ala	missense_variant	1/13	ENST00000251047.6	NP_005561.1	P49257A0A024R2A7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMAN1	ENST00000251047.6 linkuse as main transcript	c.116T>C	p.Val39Ala	missense_variant	1/13	1	NM_005570.4	ENSP00000251047.4		P49257
LMAN1	ENST00000587561.1 linkuse as main transcript	n.137T>C		non_coding_transcript_exon_variant	1/5	2

Frequencies

GnomAD3 genomes

AF:

0.0932

AC:

14178

AN:

152134

Hom.:

796

Cov.:

show subpopulations

Gnomad AFR

AF:

0.138

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.0775

Gnomad ASJ

AF:

0.100

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0404

Gnomad FIN

AF:

0.0311

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.0896

Gnomad OTH

AF:

0.103

GnomAD3 exomes

AF:

0.0685

AC:

17210

AN:

251136

Hom.:

791

AF XY:

0.0678

AC XY:

9208

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.140

Gnomad AMR exome

AF:

0.0473

Gnomad ASJ exome

AF:

0.106

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0390

Gnomad FIN exome

AF:

0.0353

Gnomad NFE exome

AF:

0.0863

Gnomad OTH exome

AF:

0.0776

GnomAD4 exome

AF:

0.0825

AC:

120535

AN:

1461738

Hom.:

5357

Cov.:

AF XY:

0.0814

AC XY:

59200

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.146

Gnomad4 AMR exome

AF:

0.0512

Gnomad4 ASJ exome

AF:

0.108

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0427

Gnomad4 FIN exome

AF:

0.0365

Gnomad4 NFE exome

AF:

0.0890

Gnomad4 OTH exome

AF:

0.0844

GnomAD4 genome

AF:

0.0932

AC:

14186

AN:

152252

Hom.:

797

Cov.:

AF XY:

0.0891

AC XY:

6633

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.138

Gnomad4 AMR

AF:

0.0774

Gnomad4 ASJ

AF:

0.100

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.0396

Gnomad4 FIN

AF:

0.0311

Gnomad4 NFE

AF:

0.0896

Gnomad4 OTH

AF:

0.101

Alfa

AF:

0.0941

Hom.:

880

Bravo

AF:

0.0984

TwinsUK

AF:

0.0863

AC:

320

ALSPAC

AF:

0.0929

AC:

358

ESP6500AA

AF:

0.129

AC:

567

ESP6500EA

AF:

0.0865

AC:

744

ExAC

AF:

0.0698

AC:

8474

Asia WGS

AF:

0.0310

AC:

109

AN:

3478

EpiCase

AF:

0.0960

EpiControl

AF:

0.0959

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	GeneDx	Jun 09, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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

0.053

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.73

CADD

Benign

4.1

DANN

Benign

0.43

DEOGEN2

Benign

0.072

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.00047

LIST_S2

Benign

0.19

MetaRNN

Benign

0.0017

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PrimateAI

Uncertain

0.49

PROVEAN

Benign

0.81

REVEL

Benign

0.028

Sift

Benign

1.0

Sift4G

Benign

0.70

Polyphen

0.0

Vest4

0.021

MPC

0.24

ClinPred

0.0020

GERP RS

-5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.018

gMVP

0.31

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

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