rs1127220

Positions:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_005570.4(LMAN1):c.351A>G(p.Arg117=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 1,613,814 control chromosomes in the GnomAD database, including 52,145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4241 hom., cov: 32)

Exomes 𝑓: 0.25 ( 47904 hom. )

Consequence

LMAN1
NM_005570.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.229

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 -16 ACMG points.

BP6

Variant 18-59355522-T-C is Benign according to our data. Variant chr18-59355522-T-C is described in ClinVar as [Benign]. Clinvar id is 259795.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.264 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.351A>G	p.Arg117=	synonymous_variant	2/13	ENST00000251047.6	NP_005561.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMAN1	ENST00000251047.6 linkuse as main transcript	c.351A>G	p.Arg117=	synonymous_variant	2/13	1	NM_005570.4	ENSP00000251047	P1
LMAN1	ENST00000587561.1 linkuse as main transcript	n.372A>G		non_coding_transcript_exon_variant	2/5	2

Frequencies

GnomAD3 genomes

AF:

0.231

AC:

35162

AN:

151964

Hom.:

4237

Cov.:

show subpopulations

Gnomad AFR

AF:

0.205

Gnomad AMI

AF:

0.173

Gnomad AMR

AF:

0.248

Gnomad ASJ

AF:

0.254

Gnomad EAS

AF:

0.0297

Gnomad SAS

AF:

0.184

Gnomad FIN

AF:

0.196

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.267

Gnomad OTH

AF:

0.235

GnomAD3 exomes

AF:

0.221

AC:

55578

AN:

251442

Hom.:

6654

AF XY:

0.223

AC XY:

30306

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.202

Gnomad AMR exome

AF:

0.215

Gnomad ASJ exome

AF:

0.251

Gnomad EAS exome

AF:

0.0275

Gnomad SAS exome

AF:

0.192

Gnomad FIN exome

AF:

0.200

Gnomad NFE exome

AF:

0.265

Gnomad OTH exome

AF:

0.234

GnomAD4 exome

AF:

0.251

AC:

367525

AN:

1461732

Hom.:

47904

Cov.:

AF XY:

0.250

AC XY:

182112

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.204

Gnomad4 AMR exome

AF:

0.221

Gnomad4 ASJ exome

AF:

0.254

Gnomad4 EAS exome

AF:

0.0204

Gnomad4 SAS exome

AF:

0.199

Gnomad4 FIN exome

AF:

0.202

Gnomad4 NFE exome

AF:

0.270

Gnomad4 OTH exome

AF:

0.233

GnomAD4 genome

AF:

0.231

AC:

35170

AN:

152082

Hom.:

4241

Cov.:

AF XY:

0.227

AC XY:

16867

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.205

Gnomad4 AMR

AF:

0.249

Gnomad4 ASJ

AF:

0.254

Gnomad4 EAS

AF:

0.0295

Gnomad4 SAS

AF:

0.184

Gnomad4 FIN

AF:

0.196

Gnomad4 NFE

AF:

0.267

Gnomad4 OTH

AF:

0.232

Alfa

AF:

0.256

Hom.:

3524

Bravo

AF:

0.232

Asia WGS

AF:

0.116

AC:

405

AN:

3478

EpiCase

AF:

0.268

EpiControl

AF:

0.267

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	clinical testing	GeneDx	Jun 09, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.44

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.44

Position offset: 5

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