rs1127220

Variant names:

• chr18-59355522-T-C
• rs1127220
• NM_005570.4:c.351A>G

Your query was ambiguous. Multiple possible variants found:

• chr18-59355522-T-C
• chr18-59355522-T-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_005570.4(LMAN1):​c.351A>G​(p.Arg117Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 1,613,814 control chromosomes in the GnomAD database, including 52,145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.23 (4241 hom., cov: 32)
  • Exomes 𝑓: 0.25 (47904 hom.)
• Consequence: LMAN1 NM_005570.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.229

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 -16 ACMG points.

• BP6: Variant 18-59355522-T-C is Benign according to our data. Variant chr18-59355522-T-C is described in ClinVar as [Benign]. Clinvar id is 259795.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMAN1	NM_005570.4	c.351A>G	p.Arg117Arg	synonymous_variant	Exon 2 of 13	ENST00000251047.6	NP_005561.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMAN1	ENST00000251047.6	c.351A>G	p.Arg117Arg	synonymous_variant	Exon 2 of 13	1	NM_005570.4	ENSP00000251047.4
LMAN1	ENST00000587561.1	n.372A>G		non_coding_transcript_exon_variant	Exon 2 of 5	2

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35162 AN: 151964 Hom.: 4237 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.248

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.0297

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.235

GnomAD3 exomes AF: 0.221 AC: 55578 AN: 251442 Hom.: 6654 AF XY: 0.223 AC XY: 30306 AN XY: 135896

Gnomad AFR exome AF: 0.202

Gnomad AMR exome AF: 0.215

Gnomad ASJ exome AF: 0.251

Gnomad EAS exome AF: 0.0275

Gnomad SAS exome AF: 0.192

Gnomad FIN exome AF: 0.200

Gnomad NFE exome AF: 0.265

Gnomad OTH exome AF: 0.234

GnomAD4 exome AF: 0.251 AC: 367525 AN: 1461732 Hom.: 47904 Cov.: 37 AF XY: 0.250 AC XY: 182112 AN XY: 727168

Gnomad4 AFR exome AF: 0.204

Gnomad4 AMR exome AF: 0.221

Gnomad4 ASJ exome AF: 0.254

Gnomad4 EAS exome AF: 0.0204

Gnomad4 SAS exome AF: 0.199

Gnomad4 FIN exome AF: 0.202

Gnomad4 NFE exome AF: 0.270

Gnomad4 OTH exome AF: 0.233

GnomAD4 genome AF: 0.231 AC: 35170 AN: 152082 Hom.: 4241 Cov.: 32 AF XY: 0.227 AC XY: 16867 AN XY: 74350

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.0295

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.196

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.232

Alfa AF: 0.256 Hom.: 3524

Bravo AF: 0.232

Asia WGS AF: 0.116 AC: 405 AN: 3478

EpiCase AF: 0.268

EpiControl AF: 0.267

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Factor V and factor VIII, combined deficiency of, type 1 Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	16
DANN	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.44		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.44		Position offset: 5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1127220; hg19: chr18-57022754; COSMIC: COSV51825716; COSMIC: COSV51825716;