chr16-954694-A-G

Variant names:

• chr16-954694-A-G
• rs3751666
• NM_022773.4:c.194-28T>C

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.194-28T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 1,559,114 control chromosomes in the GnomAD database, including 138,846 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (20609 hom., cov: 34)
  • Exomes 𝑓: 0.40 (118237 hom.)
• Consequence: LMF1 NM_022773.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.15
• 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: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics, Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 16-954694-A-G is Benign according to our data. Variant chr16-954694-A-G is described in ClinVar as Benign. ClinVar VariationId is 1275485.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.735 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.194-28T>C		intron	N/A	NP_073610.2	Q96S06-1
	LMF1	NM_001352020.1		c.194-28T>C		intron	N/A	NP_001338949.1
	LMF1	NM_001352019.2		c.-134-28T>C		intron	N/A	NP_001338948.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMF1	ENST00000262301.16	TSL:5 MANE Select	c.194-28T>C		intron	N/A	ENSP00000262301.12	Q96S06-1
	LMF1	ENST00000963976.1		c.194-28T>C		intron	N/A	ENSP00000634035.1
	LMF1	ENST00000568897.5	TSL:5	c.-451-28T>C		intron	N/A	ENSP00000458135.1	H3BVI4

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74904 AN: 152052 Hom.: 20560 Cov.: 34

Gnomad AFR AF: 0.742

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.469

GnomAD2 exomes AF: 0.444 AC: 90811 AN: 204676 AF XY: 0.438

Gnomad AFR exome AF: 0.752

Gnomad AMR exome AF: 0.498

Gnomad ASJ exome AF: 0.322

Gnomad EAS exome AF: 0.402

Gnomad FIN exome AF: 0.324

Gnomad NFE exome AF: 0.380

Gnomad OTH exome AF: 0.418

GnomAD4 exome AF: 0.402 AC: 565134 AN: 1406944 Hom.: 118237 Cov.: 32 AF XY: 0.405 AC XY: 280881 AN XY: 693888

African (AFR) AF: 0.765 AC: 24573 AN: 32140

American (AMR) AF: 0.499 AC: 20081 AN: 40230

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 7243 AN: 22736

East Asian (EAS) AF: 0.380 AC: 14925 AN: 39266

South Asian (SAS) AF: 0.574 AC: 44366 AN: 77270

European-Finnish (FIN) AF: 0.327 AC: 15091 AN: 46216

Middle Eastern (MID) AF: 0.406 AC: 2224 AN: 5482

European-Non Finnish (NFE) AF: 0.380 AC: 412616 AN: 1085416

Other (OTH) AF: 0.413 AC: 24015 AN: 58188

GnomAD4 genome AF: 0.493 AC: 75011 AN: 152170 Hom.: 20609 Cov.: 34 AF XY: 0.489 AC XY: 36394 AN XY: 74412

African (AFR) AF: 0.742 AC: 30818 AN: 41516

American (AMR) AF: 0.478 AC: 7306 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1154 AN: 3462

East Asian (EAS) AF: 0.397 AC: 2056 AN: 5180

South Asian (SAS) AF: 0.594 AC: 2863 AN: 4818

European-Finnish (FIN) AF: 0.309 AC: 3279 AN: 10598

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.383 AC: 26008 AN: 67992

Other (OTH) AF: 0.468 AC: 988 AN: 2112

Alfa AF: 0.423 Hom.: 35420

Bravo AF: 0.512

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0060
DANN	Benign	0.22
PhyloP100		-3.1
Mutation Taster		=100/0	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: rs3751666; hg19: chr16-1004694; COSMIC: COSV51902212;