18-59342224-C-T

Position:

• chr18-59342224-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005570.4(LMAN1):​c.956-3271G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 151,856 control chromosomes in the GnomAD database, including 39,686 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.72 (39686 hom., cov: 30)
• Consequence: LMAN1 NM_005570.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.627

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMAN1	NM_005570.4	c.956-3271G>A		intron_variant		ENST00000251047.6	NP_005561.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMAN1	ENST00000251047.6	c.956-3271G>A		intron_variant		1	NM_005570.4	ENSP00000251047.4

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109277 AN: 151738 Hom.: 39621 Cov.: 30

Gnomad AFR AF: 0.799

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.644

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.721

Gnomad OTH AF: 0.704

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.720 AC: 109402 AN: 151856 Hom.: 39686 Cov.: 30 AF XY: 0.713 AC XY: 52940 AN XY: 74220

Gnomad4 AFR AF: 0.799

Gnomad4 AMR AF: 0.667

Gnomad4 ASJ AF: 0.713

Gnomad4 EAS AF: 0.505

Gnomad4 SAS AF: 0.646

Gnomad4 FIN AF: 0.648

Gnomad4 NFE AF: 0.721

Gnomad4 OTH AF: 0.704

Alfa AF: 0.717 Hom.: 4630

Bravo AF: 0.723

Asia WGS AF: 0.616 AC: 2143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.7
DANN	Benign	0.68

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: rs12953981; hg19: chr18-57009456;