NM_021819.3:c.1200-5G>A

Variant names:

• chr15-74823554-G-A
• rs7162232
• NM_021819.3:c.1200-5G>A

Variant summary

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

The NM_021819.3(LMAN1L):​c.1200-5G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.699 in 1,612,692 control chromosomes in the GnomAD database, including 397,391 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.66 (33328 hom., cov: 31)
  • Exomes 𝑓: 0.70 (364063 hom.)
• Consequence: LMAN1L NM_021819.3 splice_region, intron
• Scores: Splicing: ADA: 0.000009080
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60
• Publications: 34 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=-0.98).
• 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.1200-5G>A		splice_region_variant, intron_variant	Intron 11 of 13	ENST00000309664.10	NP_068591.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMAN1L	ENST00000309664.10	c.1200-5G>A		splice_region_variant, intron_variant	Intron 11 of 13	1	NM_021819.3	ENSP00000310431.5

Frequencies

GnomAD3 genomes AF: 0.659 AC: 99984 AN: 151766 Hom.: 33310 Cov.: 31

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.707

Gnomad AMR AF: 0.531

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.604

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.670

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.640

GnomAD2 exomes AF: 0.657 AC: 164823 AN: 250840 AF XY: 0.664

Gnomad AFR exome AF: 0.606

Gnomad AMR exome AF: 0.484

Gnomad ASJ exome AF: 0.705

Gnomad EAS exome AF: 0.609

Gnomad FIN exome AF: 0.673

Gnomad NFE exome AF: 0.716

Gnomad OTH exome AF: 0.683

GnomAD4 exome AF: 0.704 AC: 1027679 AN: 1460808 Hom.: 364063 Cov.: 42 AF XY: 0.703 AC XY: 510606 AN XY: 726786

African (AFR) AF: 0.610 AC: 20423 AN: 33456

American (AMR) AF: 0.489 AC: 21871 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.704 AC: 18376 AN: 26104

East Asian (EAS) AF: 0.584 AC: 23164 AN: 39690

South Asian (SAS) AF: 0.655 AC: 56517 AN: 86226

European-Finnish (FIN) AF: 0.670 AC: 35601 AN: 53154

Middle Eastern (MID) AF: 0.700 AC: 4034 AN: 5760

European-Non Finnish (NFE) AF: 0.725 AC: 805398 AN: 1111382

Other (OTH) AF: 0.701 AC: 42295 AN: 60348

GnomAD4 genome AF: 0.659 AC: 100049 AN: 151884 Hom.: 33328 Cov.: 31 AF XY: 0.653 AC XY: 48453 AN XY: 74224

African (AFR) AF: 0.614 AC: 25404 AN: 41368

American (AMR) AF: 0.531 AC: 8100 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.694 AC: 2407 AN: 3468

East Asian (EAS) AF: 0.604 AC: 3097 AN: 5128

South Asian (SAS) AF: 0.663 AC: 3188 AN: 4812

European-Finnish (FIN) AF: 0.670 AC: 7086 AN: 10574

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.715 AC: 48556 AN: 67950

Other (OTH) AF: 0.642 AC: 1355 AN: 2112

Alfa AF: 0.693 Hom.: 117282

Bravo AF: 0.648

Asia WGS AF: 0.677 AC: 2353 AN: 3478

EpiCase AF: 0.705

EpiControl AF: 0.708

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.11
DANN	Benign	0.42
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0000091
dbscSNV1_RF	Benign	0.0
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: rs7162232; hg19: chr15-75115895; COSMIC: COSV59001700; COSMIC: COSV59001700;