Variant chr18-59338423-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_005570.4(LMAN1):c.1220+134A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 730,178 control chromosomes in the GnomAD database, including 25,527 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.25 ( 4869 hom., cov: 32)

Exomes 𝑓: 0.26 ( 20658 hom. )

Consequence

LMAN1
NM_005570.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.242

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 18-59338423-T-C is Benign according to our data. Variant chr18-59338423-T-C is described in ClinVar as [Benign]. Clinvar id is 1244869.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.349 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.1220+134A>G		intron_variant		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.1220+134A>G		intron_variant		1	NM_005570.4	ENSP00000251047	P1

Frequencies

GnomAD3 genomes

AF:

0.251

AC:

38174

AN:

151980

Hom.:

4865

Cov.:

show subpopulations

Gnomad AFR

AF:

0.246

Gnomad AMI

AF:

0.155

Gnomad AMR

AF:

0.194

Gnomad ASJ

AF:

0.295

Gnomad EAS

AF:

0.275

Gnomad SAS

AF:

0.362

Gnomad FIN

AF:

0.229

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.260

Gnomad OTH

AF:

0.242

GnomAD4 exome

AF:

0.262

AC:

151725

AN:

578080

Hom.:

20658

AF XY:

0.268

AC XY:

82867

AN XY:

309730

show subpopulations

Gnomad4 AFR exome

AF:

0.253

Gnomad4 AMR exome

AF:

0.162

Gnomad4 ASJ exome

AF:

0.298

Gnomad4 EAS exome

AF:

0.259

Gnomad4 SAS exome

AF:

0.345

Gnomad4 FIN exome

AF:

0.229

Gnomad4 NFE exome

AF:

0.259

Gnomad4 OTH exome

AF:

0.266

GnomAD4 genome

AF:

0.251

AC:

38200

AN:

152098

Hom.:

4869

Cov.:

AF XY:

0.250

AC XY:

18560

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.246

Gnomad4 AMR

AF:

0.194

Gnomad4 ASJ

AF:

0.295

Gnomad4 EAS

AF:

0.275

Gnomad4 SAS

AF:

0.363

Gnomad4 FIN

AF:

0.229

Gnomad4 NFE

AF:

0.260

Gnomad4 OTH

AF:

0.241

Alfa

AF:

0.254

Hom.:

3764

Bravo

AF:

0.244

Asia WGS

AF:

0.336

AC:

1167

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

5.8

DANN

Benign

0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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