rs4984948

Variant names:

• chr16-854551-G-C
• rs4984948
• NM_022773.4:c.1685C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-854551-G-C
• chr16-854551-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_022773.4(LMF1):​c.1685C>G​(p.Pro562Arg) variant causes a missense change. The variant allele was found at a frequency of 0.02 in 1,608,040 control chromosomes in the GnomAD database, including 1,477 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (225 hom., cov: 33)
  • Exomes 𝑓: 0.019 (1252 hom.)
• Consequence: LMF1 NM_022773.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 4.50
• Publications: 25 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

ENSG00000287855 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017978847).
• BP6: Variant 16-854551-G-C is Benign according to our data. Variant chr16-854551-G-C is described in ClinVar as Benign. ClinVar VariationId is 1277320.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.131 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.1685C>G	p.Pro562Arg	missense	Exon 11 of 11	NP_073610.2	Q96S06-1
	LMF1	NM_001352019.2		c.1358C>G	p.Pro453Arg	missense	Exon 11 of 11	NP_001338948.1
	LMF1	NM_001352018.2		c.1286C>G	p.Pro429Arg	missense	Exon 12 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.1685C>G	p.Pro562Arg	missense	Exon 11 of 11	ENSP00000262301.12	Q96S06-1
	LMF1	ENST00000565276.5	TSL:1	n.*680C>G		non_coding_transcript_exon	Exon 3 of 3	ENSP00000455930.1	H3BQT4
	LMF1	ENST00000565276.5	TSL:1	n.*680C>G		3_prime_UTR	Exon 3 of 3	ENSP00000455930.1	H3BQT4

Frequencies

GnomAD3 genomes AF: 0.0261 AC: 3977 AN: 152166 Hom.: 222 Cov.: 33

Gnomad AFR AF: 0.00799

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.0524

Gnomad FIN AF: 0.0130

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00713

Gnomad OTH AF: 0.0292

GnomAD2 exomes AF: 0.0468 AC: 11050 AN: 236352 AF XY: 0.0412

Gnomad AFR exome AF: 0.00605

Gnomad AMR exome AF: 0.175

Gnomad ASJ exome AF: 0.00747

Gnomad EAS exome AF: 0.137

Gnomad FIN exome AF: 0.0111

Gnomad NFE exome AF: 0.00683

Gnomad OTH exome AF: 0.0329

GnomAD4 exome AF: 0.0193 AC: 28119 AN: 1455756 Hom.: 1252 Cov.: 31 AF XY: 0.0197 AC XY: 14250 AN XY: 724096

African (AFR) AF: 0.00667 AC: 223 AN: 33444

American (AMR) AF: 0.168 AC: 7412 AN: 44084

Ashkenazi Jewish (ASJ) AF: 0.00683 AC: 178 AN: 26046

East Asian (EAS) AF: 0.129 AC: 5094 AN: 39560

South Asian (SAS) AF: 0.0517 AC: 4430 AN: 85662

European-Finnish (FIN) AF: 0.0106 AC: 529 AN: 49928

Middle Eastern (MID) AF: 0.00486 AC: 28 AN: 5762

European-Non Finnish (NFE) AF: 0.00807 AC: 8967 AN: 1111078

Other (OTH) AF: 0.0209 AC: 1258 AN: 60192

GnomAD4 genome AF: 0.0262 AC: 3984 AN: 152284 Hom.: 225 Cov.: 33 AF XY: 0.0300 AC XY: 2231 AN XY: 74452

African (AFR) AF: 0.00796 AC: 331 AN: 41570

American (AMR) AF: 0.128 AC: 1958 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00778 AC: 27 AN: 3472

East Asian (EAS) AF: 0.140 AC: 722 AN: 5160

South Asian (SAS) AF: 0.0523 AC: 252 AN: 4820

European-Finnish (FIN) AF: 0.0130 AC: 138 AN: 10630

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00713 AC: 485 AN: 68006

Other (OTH) AF: 0.0294 AC: 62 AN: 2110

Alfa AF: 0.00983 Hom.: 5

Bravo AF: 0.0332

TwinsUK AF: 0.00836 AC: 31

ALSPAC AF: 0.00934 AC: 36

ESP6500AA AF: 0.00615 AC: 24

ESP6500EA AF: 0.00910 AC: 75

ExAC AF: 0.0371 AC: 4454

Asia WGS AF: 0.0760 AC: 264 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
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.27	T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.54	T
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-1.2	T
MutationAssessor	Uncertain	2.9	M
PhyloP100		4.5
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.25
Sift	Benign	0.084	T
Sift4G	Benign	0.19	T
Polyphen		0.75	P
Vest4		0.19
MPC		0.10
ClinPred		0.032	T
GERP RS		4.4
Varity_R		0.30
gMVP		0.62
Mutation Taster		=89/11	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4984948; hg19: chr16-904551; COSMIC: COSV51894821;