Variant 18-59328688-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005570.4(LMAN1):c.*2405C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0544 in 151,972 control chromosomes in the GnomAD database, including 300 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.054 ( 300 hom., cov: 32)

Exomes 𝑓: 0.25 ( 0 hom. )

Consequence

LMAN1
NM_005570.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.193

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 (BayesDel_noAF=-0.82).

BP6

Variant 18-59328688-G-T is Benign according to our data. Variant chr18-59328688-G-T is described in ClinVar as [Benign]. Clinvar id is 327544.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMAN1	NM_005570.4 linkuse as main transcript	c.*2405C>A		3_prime_UTR_variant	13/13	ENST00000251047.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMAN1	ENST00000251047.6 linkuse as main transcript	c.*2405C>A		3_prime_UTR_variant	13/13	1	NM_005570.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0545

AC:

8281

AN:

151850

Hom.:

302

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0152

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.0569

Gnomad ASJ

AF:

0.0905

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.0399

Gnomad FIN

AF:

0.0313

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.0842

Gnomad OTH

AF:

0.0696

GnomAD4 exome

AF:

0.250

AC:

AN:

Hom.:

Cov.:

AF XY:

0.250

AC XY:

AN XY:

show subpopulations

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.500

GnomAD4 genome

AF:

0.0544

AC:

8269

AN:

151968

Hom.:

300

Cov.:

AF XY:

0.0516

AC XY:

3829

AN XY:

74248

show subpopulations

Gnomad4 AFR

AF:

0.0153

Gnomad4 AMR

AF:

0.0568

Gnomad4 ASJ

AF:

0.0905

Gnomad4 EAS

AF:

0.000388

Gnomad4 SAS

AF:

0.0389

Gnomad4 FIN

AF:

0.0313

Gnomad4 NFE

AF:

0.0842

Gnomad4 OTH

AF:

0.0680

Alfa

AF:

0.0647

Hom.:

Bravo

AF:

0.0536

Asia WGS

AF:

0.0180

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.7

DANN

Benign

0.67

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