chr18-59329030-G-C

Position:

• chr18-59329030-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005570.4(LMAN1):​c.*2063C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0957 in 152,150 control chromosomes in the GnomAD database, including 850 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.096 (850 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: LMAN1 NM_005570.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0690

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 18-59329030-G-C is Benign according to our data. Variant chr18-59329030-G-C is described in ClinVar as [Benign]. Clinvar id is 327548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMAN1	NM_005570.4	c.*2063C>G		3_prime_UTR_variant	13/13	ENST00000251047.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMAN1	ENST00000251047.6	c.*2063C>G		3_prime_UTR_variant	13/13	1	NM_005570.4	P1

Frequencies

GnomAD3 genomes AF: 0.0958 AC: 14565 AN: 152032 Hom.: 850 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.0363

Gnomad AMR AF: 0.0785

Gnomad ASJ AF: 0.100

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0400

Gnomad FIN AF: 0.0314

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0896

Gnomad OTH AF: 0.105

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.0957 AC: 14567 AN: 152150 Hom.: 850 Cov.: 32 AF XY: 0.0917 AC XY: 6823 AN XY: 74398

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.0783

Gnomad4 ASJ AF: 0.100

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0392

Gnomad4 FIN AF: 0.0314

Gnomad4 NFE AF: 0.0896

Gnomad4 OTH AF: 0.103

Alfa AF: 0.0376 Hom.: 27

Bravo AF: 0.101

Asia WGS AF: 0.0310 AC: 108 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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 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. -

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	-0.79
CADD	Benign	6.9
DANN	Benign	0.75

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

Other links and lift over

dbSNP: rs7239187; hg19: chr18-56996262;