15-74823843-C-G

Variant names:

• chr15-74823843-C-G
• rs11634474
• NM_021819.3:c.1323+161C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021819.3(LMAN1L):​c.1323+161C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 734,308 control chromosomes in the GnomAD database, including 173,144 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 0.66 (33018 hom., cov: 31)
  • Exomes 𝑓: 0.69 (140126 hom.)
• Consequence: LMAN1L NM_021819.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.384
• Publications: 17 publications found

Genes affected

LMAN1L (HGNC:6632): (lectin, mannose binding 1 like) This gene encodes a mannose-binding type 1 transmembrane protein that contains an N-terminal lectin-like carbohydrate recognition domain. The encoded protein is similar in structure to lectins found in leguminous plants. This lectin is thought to transport newly synthesized glycoproteins from the endoplasmic reticulum (ER) to the ER-Golgi intermediate compartment. [provided by RefSeq, Jan 2017]

ENSG00000261606 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMAN1L	NM_021819.3	c.1323+161C>G		intron_variant	Intron 12 of 13	ENST00000309664.10	NP_068591.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMAN1L	ENST00000309664.10	c.1323+161C>G		intron_variant	Intron 12 of 13	1	NM_021819.3	ENSP00000310431.5

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99524 AN: 151848 Hom.: 33007 Cov.: 31

Gnomad AFR AF: 0.605

Gnomad AMI AF: 0.707

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.677

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.670

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.714

Gnomad OTH AF: 0.635

GnomAD4 exome AF: 0.690 AC: 401976 AN: 582342 Hom.: 140126 Cov.: 8 AF XY: 0.689 AC XY: 208176 AN XY: 301932

African (AFR) AF: 0.603 AC: 9086 AN: 15072

American (AMR) AF: 0.503 AC: 10662 AN: 21176

Ashkenazi Jewish (ASJ) AF: 0.693 AC: 10166 AN: 14664

East Asian (EAS) AF: 0.579 AC: 18567 AN: 32050

South Asian (SAS) AF: 0.655 AC: 32831 AN: 50100

European-Finnish (FIN) AF: 0.666 AC: 20450 AN: 30688

Middle Eastern (MID) AF: 0.661 AC: 1477 AN: 2236

European-Non Finnish (NFE) AF: 0.720 AC: 277827 AN: 385922

Other (OTH) AF: 0.687 AC: 20910 AN: 30434

GnomAD4 genome AF: 0.655 AC: 99581 AN: 151966 Hom.: 33018 Cov.: 31 AF XY: 0.649 AC XY: 48196 AN XY: 74218

African (AFR) AF: 0.605 AC: 25080 AN: 41434

American (AMR) AF: 0.526 AC: 8046 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.677 AC: 2348 AN: 3466

East Asian (EAS) AF: 0.605 AC: 3112 AN: 5142

South Asian (SAS) AF: 0.664 AC: 3193 AN: 4812

European-Finnish (FIN) AF: 0.670 AC: 7083 AN: 10570

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.714 AC: 48527 AN: 67942

Other (OTH) AF: 0.637 AC: 1340 AN: 2104

Alfa AF: 0.594 Hom.: 1894

Bravo AF: 0.644

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.9
DANN	Benign	0.40
PhyloP100		0.38
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs11634474; hg19: chr15-75116184; COSMIC: COSV59001718; COSMIC: COSV59001718;