chr15-74815539-A-C

Variant names:

• chr15-74815539-A-C
• rs7176022
• NM_021819.3:c.176-618A>C

Variant summary

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

The NM_021819.3(LMAN1L):​c.176-618A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.657 in 152,084 control chromosomes in the GnomAD database, including 33,249 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 (33249 hom., cov: 33)
• Consequence: LMAN1L NM_021819.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 21 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.709 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021819.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMAN1L	NM_021819.3	MANE Select	c.176-618A>C		intron	N/A	NP_068591.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMAN1L	ENST00000309664.10	TSL:1 MANE Select	c.176-618A>C		intron	N/A	ENSP00000310431.5
	LMAN1L	ENST00000379709.7	TSL:1	c.176-618A>C		intron	N/A	ENSP00000369031.3
	LMAN1L	ENST00000470711.6	TSL:1	n.229-618A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.657 AC: 99908 AN: 151966 Hom.: 33241 Cov.: 33

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.707

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.604

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.637

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

GnomAD4 genome AF: 0.657 AC: 99962 AN: 152084 Hom.: 33249 Cov.: 33 AF XY: 0.651 AC XY: 48425 AN XY: 74340

African (AFR) AF: 0.611 AC: 25320 AN: 41470

American (AMR) AF: 0.528 AC: 8065 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.691 AC: 2400 AN: 3472

East Asian (EAS) AF: 0.603 AC: 3123 AN: 5178

South Asian (SAS) AF: 0.657 AC: 3167 AN: 4820

European-Finnish (FIN) AF: 0.671 AC: 7093 AN: 10570

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.715 AC: 48587 AN: 67982

Other (OTH) AF: 0.639 AC: 1350 AN: 2114

Alfa AF: 0.651 Hom.: 8120

Bravo AF: 0.646

Asia WGS AF: 0.672 AC: 2338 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.36
DANN	Benign	0.46
PhyloP100		-1.0
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: rs7176022; hg19: chr15-75107880;