Variant rs2298712 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.1374+20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 1,592,906 control chromosomes in the GnomAD database, including 78,697 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 9402 hom., cov: 32)

Exomes 𝑓: 0.31 ( 69295 hom. )

Consequence

LMAN1
NM_005570.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.770

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=-0.83).

BP6

Variant 18-59333071-G-A is Benign according to our data. Variant chr18-59333071-G-A is described in ClinVar as [Benign]. Clinvar id is 259793.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-59333071-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.439 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.1374+20C>T		intron_variant		ENST00000251047.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMAN1	ENST00000251047.6 linkuse as main transcript	c.1374+20C>T		intron_variant		1	NM_005570.4	P1
LMAN1	ENST00000587918.1 linkuse as main transcript	n.601+20C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.344

AC:

52165

AN:

151746

Hom.:

9385

Cov.:

show subpopulations

Gnomad AFR

AF:

0.445

Gnomad AMI

AF:

0.183

Gnomad AMR

AF:

0.252

Gnomad ASJ

AF:

0.352

Gnomad EAS

AF:

0.268

Gnomad SAS

AF:

0.387

Gnomad FIN

AF:

0.328

Gnomad MID

AF:

0.291

Gnomad NFE

AF:

0.311

Gnomad OTH

AF:

0.326

GnomAD3 exomes

AF:

0.308

AC:

76999

AN:

249612

Hom.:

12680

AF XY:

0.313

AC XY:

42289

AN XY:

134956

show subpopulations

Gnomad AFR exome

AF:

0.450

Gnomad AMR exome

AF:

0.181

Gnomad ASJ exome

AF:

0.350

Gnomad EAS exome

AF:

0.273

Gnomad SAS exome

AF:

0.388

Gnomad FIN exome

AF:

0.316

Gnomad NFE exome

AF:

0.306

Gnomad OTH exome

AF:

0.316

GnomAD4 exome

AF:

0.306

AC:

441094

AN:

1441042

Hom.:

69295

Cov.:

AF XY:

0.308

AC XY:

221398

AN XY:

718108

show subpopulations

Gnomad4 AFR exome

AF:

0.457

Gnomad4 AMR exome

AF:

0.190

Gnomad4 ASJ exome

AF:

0.345

Gnomad4 EAS exome

AF:

0.258

Gnomad4 SAS exome

AF:

0.375

Gnomad4 FIN exome

AF:

0.320

Gnomad4 NFE exome

AF:

0.300

Gnomad4 OTH exome

AF:

0.325

GnomAD4 genome

AF:

0.344

AC:

52221

AN:

151864

Hom.:

9402

Cov.:

AF XY:

0.341

AC XY:

25334

AN XY:

74222

show subpopulations

Gnomad4 AFR

AF:

0.445

Gnomad4 AMR

AF:

0.251

Gnomad4 ASJ

AF:

0.352

Gnomad4 EAS

AF:

0.268

Gnomad4 SAS

AF:

0.388

Gnomad4 FIN

AF:

0.328

Gnomad4 NFE

AF:

0.311

Gnomad4 OTH

AF:

0.324

Alfa

AF:

0.324

Hom.:

2915

Bravo

AF:

0.340

Asia WGS

AF:

0.357

AC:

1240

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

DANN

Benign

0.52

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