rs7162232

chr15-74823554-G-Achr15-74823554-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021819.3(LMAN1L):c.1200-5G>A variant causes a splice region, splice polypyrimidine tract, 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, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.000009080
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.60

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
LMAN1L	NM_021819.3	c.1200-5G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000309664.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMAN1L	ENST00000309664.10	c.1200-5G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_021819.3	P1
LMAN1L	ENST00000379709.7	c.1164-5G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1
LMAN1L	ENST00000567848.1	c.242+845G>A		intron_variant		4
LMAN1L	ENST00000565585.5	n.1594-5G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2

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

GnomAD3 exomes AF: 0.657 AC: 164823 AN: 250840 Hom.: 55164 AF XY: 0.664 AC XY: 90018 AN XY: 135588

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 SAS exome AF: 0.656

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

Gnomad4 AFR exome AF: 0.610

Gnomad4 AMR exome AF: 0.489

Gnomad4 ASJ exome AF: 0.704

Gnomad4 EAS exome AF: 0.584

Gnomad4 SAS exome AF: 0.655

Gnomad4 FIN exome AF: 0.670

Gnomad4 NFE exome AF: 0.725

Gnomad4 OTH exome AF: 0.701

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

Gnomad4 AFR AF: 0.614

Gnomad4 AMR AF: 0.531

Gnomad4 ASJ AF: 0.694

Gnomad4 EAS AF: 0.604

Gnomad4 SAS AF: 0.663

Gnomad4 FIN AF: 0.670

Gnomad4 NFE AF: 0.715

Gnomad4 OTH AF: 0.642

Alfa AF: 0.701 Hom.: 73505

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs7162232; hg19: chr15-75115895; COSMIC: COSV59001700; COSMIC: COSV59001700;