rs11248955

Variant names:

• chr16-934113-C-A
• rs11248955
• NM_022773.4:c.514+131G>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001352018.2(LMF1):​c.-8G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 1,557,000 control chromosomes in the GnomAD database, including 87,244 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (16947 hom., cov: 33)
  • Exomes 𝑓: 0.30 (70297 hom.)
• Consequence: LMF1 NM_001352018.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.10
• Publications: 10 publications found

Genes affected

LMF1 (HGNC:14154): (lipase maturation factor 1) Involved in triglyceride metabolic process. Predicted to be integral component of membrane. Predicted to be active in endoplasmic reticulum membrane. Implicated in familial lipase maturation factor 1 deficiency. [provided by Alliance of Genome Resources, Apr 2022]

LMF1-AS1 (HGNC:50469): (LMF1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.052).
• BP6: Variant 16-934113-C-A is Benign according to our data. Variant chr16-934113-C-A is described in ClinVar as Benign. ClinVar VariationId is 1250664.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001352018.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMF1	NM_022773.4	MANE Select	c.514+131G>T		intron	N/A	NP_073610.2
	LMF1	NM_001352018.2		c.-8G>T		5_prime_UTR_premature_start_codon_gain	Exon 4 of 12	NP_001338947.1
	LMF1	NM_001352018.2		c.-8G>T		5_prime_UTR	Exon 4 of 12	NP_001338947.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMF1	ENST00000262301.16	TSL:5 MANE Select	c.514+131G>T		intron	N/A	ENSP00000262301.12
	LMF1	ENST00000963976.1		c.514+131G>T		intron	N/A	ENSP00000634035.1
	LMF1	ENST00000568897.5	TSL:5	c.-138+20240G>T		intron	N/A	ENSP00000458135.1

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64702 AN: 152002 Hom.: 16892 Cov.: 33

Gnomad AFR AF: 0.739

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.395

GnomAD2 exomes AF: 0.363 AC: 64661 AN: 178176 AF XY: 0.354

Gnomad AFR exome AF: 0.755

Gnomad AMR exome AF: 0.443

Gnomad ASJ exome AF: 0.246

Gnomad EAS exome AF: 0.385

Gnomad FIN exome AF: 0.255

Gnomad NFE exome AF: 0.283

Gnomad OTH exome AF: 0.330

GnomAD4 exome AF: 0.303 AC: 425432 AN: 1404880 Hom.: 70297 Cov.: 34 AF XY: 0.305 AC XY: 211943 AN XY: 695830

African (AFR) AF: 0.767 AC: 24969 AN: 32568

American (AMR) AF: 0.443 AC: 16791 AN: 37912

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 6244 AN: 25288

East Asian (EAS) AF: 0.360 AC: 13615 AN: 37798

South Asian (SAS) AF: 0.423 AC: 34507 AN: 81532

European-Finnish (FIN) AF: 0.244 AC: 8733 AN: 35774

Middle Eastern (MID) AF: 0.313 AC: 1776 AN: 5672

European-Non Finnish (NFE) AF: 0.275 AC: 299875 AN: 1089700

Other (OTH) AF: 0.323 AC: 18922 AN: 58636

GnomAD4 genome AF: 0.426 AC: 64816 AN: 152120 Hom.: 16947 Cov.: 33 AF XY: 0.423 AC XY: 31426 AN XY: 74364

African (AFR) AF: 0.739 AC: 30661 AN: 41476

American (AMR) AF: 0.413 AC: 6325 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 876 AN: 3470

East Asian (EAS) AF: 0.377 AC: 1948 AN: 5164

South Asian (SAS) AF: 0.441 AC: 2127 AN: 4822

European-Finnish (FIN) AF: 0.238 AC: 2526 AN: 10598

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.280 AC: 19004 AN: 67972

Other (OTH) AF: 0.392 AC: 829 AN: 2114

Alfa AF: 0.435 Hom.: 10318

Bravo AF: 0.453

Asia WGS AF: 0.446 AC: 1550 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.24
DANN	Benign	0.72
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs11248955; hg19: chr16-984113; COSMIC: COSV51896082;