chr16-911051-C-T

Variant names:

• chr16-911051-C-T
• rs2277893
• NM_022773.4:c.543G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_022773.4(LMF1):​c.543G>A​(p.Gly181Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 1,611,206 control chromosomes in the GnomAD database, including 45,350 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (8429 hom., cov: 32)
  • Exomes 𝑓: 0.21 (36921 hom.)
• Consequence: LMF1 NM_022773.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -3.07
• Publications: 24 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 Gene-Disease associations (from GenCC):

• lipase deficiency, combined

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet

LOC124903619 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 16-911051-C-T is Benign according to our data. Variant chr16-911051-C-T is described in ClinVar as Benign. ClinVar VariationId is 1278135.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.07 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022773.4. 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.543G>A	p.Gly181Gly	synonymous	Exon 4 of 11	NP_073610.2	Q96S06-1
	LMF1	NM_001352020.1		c.543G>A	p.Gly181Gly	synonymous	Exon 4 of 11	NP_001338949.1
	LMF1	NM_001352019.2		c.216G>A	p.Gly72Gly	synonymous	Exon 4 of 11	NP_001338948.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMF1	ENST00000262301.16	TSL:5 MANE Select	c.543G>A	p.Gly181Gly	synonymous	Exon 4 of 11	ENSP00000262301.12	Q96S06-1
	LMF1	ENST00000963976.1		c.543G>A	p.Gly181Gly	synonymous	Exon 4 of 12	ENSP00000634035.1
	LMF1	ENST00000570014.5	TSL:5	c.216G>A	p.Gly72Gly	synonymous	Exon 4 of 7	ENSP00000454672.1	H3BN37

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44956 AN: 151874 Hom.: 8400 Cov.: 32

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.278

GnomAD2 exomes AF: 0.263 AC: 64563 AN: 245852 AF XY: 0.259

Gnomad AFR exome AF: 0.510

Gnomad AMR exome AF: 0.398

Gnomad ASJ exome AF: 0.148

Gnomad EAS exome AF: 0.317

Gnomad FIN exome AF: 0.139

Gnomad NFE exome AF: 0.171

Gnomad OTH exome AF: 0.232

GnomAD4 exome AF: 0.206 AC: 300436 AN: 1459214 Hom.: 36921 Cov.: 33 AF XY: 0.210 AC XY: 152746 AN XY: 725814

African (AFR) AF: 0.523 AC: 17488 AN: 33420

American (AMR) AF: 0.395 AC: 17511 AN: 44316

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 4012 AN: 26126

East Asian (EAS) AF: 0.292 AC: 11562 AN: 39610

South Asian (SAS) AF: 0.417 AC: 35880 AN: 86088

European-Finnish (FIN) AF: 0.138 AC: 7262 AN: 52614

Middle Eastern (MID) AF: 0.242 AC: 1394 AN: 5768

European-Non Finnish (NFE) AF: 0.173 AC: 191689 AN: 1110972

Other (OTH) AF: 0.226 AC: 13638 AN: 60300

GnomAD4 genome AF: 0.296 AC: 45022 AN: 151992 Hom.: 8429 Cov.: 32 AF XY: 0.297 AC XY: 22097 AN XY: 74296

African (AFR) AF: 0.506 AC: 20957 AN: 41392

American (AMR) AF: 0.345 AC: 5272 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 552 AN: 3466

East Asian (EAS) AF: 0.308 AC: 1590 AN: 5168

South Asian (SAS) AF: 0.441 AC: 2127 AN: 4820

European-Finnish (FIN) AF: 0.144 AC: 1523 AN: 10594

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12013 AN: 67968

Other (OTH) AF: 0.276 AC: 584 AN: 2114

Alfa AF: 0.228 Hom.: 2207

Bravo AF: 0.318

Asia WGS AF: 0.398 AC: 1383 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Cardiovascular phenotype (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.87
DANN	Benign	0.39
PhyloP100		-3.1
Mutation Taster		=286/14	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: rs2277893; hg19: chr16-961051; COSMIC: COSV51894854;