chr18-59338423-T-C

Variant names:

• chr18-59338423-T-C
• rs10515978
• NM_005570.4:c.1220+134A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.242
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

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

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae)
• combined deficiency of factor V and factor VIII

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000267677 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
LMAN1	NM_005570.4	c.1220+134A>G		intron_variant	Intron 10 of 12	ENST00000251047.6	NP_005561.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMAN1	ENST00000251047.6	c.1220+134A>G		intron_variant	Intron 10 of 12	1	NM_005570.4	ENSP00000251047.4
ENSG00000267677	ENST00000767578.1	n.232+13833T>C		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38174 AN: 151980 Hom.: 4865 Cov.: 32

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

African (AFR) AF: 0.253 AC: 3996 AN: 15824

American (AMR) AF: 0.162 AC: 5419 AN: 33424

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 5882 AN: 19738

East Asian (EAS) AF: 0.259 AC: 8279 AN: 31992

South Asian (SAS) AF: 0.345 AC: 21269 AN: 61614

European-Finnish (FIN) AF: 0.229 AC: 8080 AN: 35270

Middle Eastern (MID) AF: 0.261 AC: 642 AN: 2462

European-Non Finnish (NFE) AF: 0.259 AC: 89912 AN: 346768

Other (OTH) AF: 0.266 AC: 8246 AN: 30988

GnomAD4 genome AF: 0.251 AC: 38200 AN: 152098 Hom.: 4869 Cov.: 32 AF XY: 0.250 AC XY: 18560 AN XY: 74336

African (AFR) AF: 0.246 AC: 10195 AN: 41498

American (AMR) AF: 0.194 AC: 2961 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1022 AN: 3468

East Asian (EAS) AF: 0.275 AC: 1423 AN: 5168

South Asian (SAS) AF: 0.363 AC: 1750 AN: 4824

European-Finnish (FIN) AF: 0.229 AC: 2420 AN: 10576

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17704 AN: 67976

Other (OTH) AF: 0.241 AC: 508 AN: 2108

Alfa AF: 0.254 Hom.: 4412

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

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.8
DANN	Benign	0.67
PhyloP100		-0.24
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10515978; hg19: chr18-57005655;