rs2076425

Variant names:

• chr16-879711-C-T
• rs2076425
• NM_022773.4:c.756G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-879711-C-T
• chr16-879711-C-G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_022773.4(LMF1):​c.756G>A​(p.Ala252Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,597,650 control chromosomes in the GnomAD database, including 13,159 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1709 hom., cov: 33)
  • Exomes 𝑓: 0.12 (11450 hom.)
• Consequence: LMF1 NM_022773.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.690
• Publications: 19 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

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 16-879711-C-T is Benign according to our data. Variant chr16-879711-C-T is described in ClinVar as Benign. ClinVar VariationId is 1279701.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.69 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.261 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.756G>A	p.Ala252Ala	synonymous	Exon 6 of 11	NP_073610.2	Q96S06-1
	LMF1	NM_001352020.1		c.756G>A	p.Ala252Ala	synonymous	Exon 6 of 11	NP_001338949.1
	LMF1	NM_001352019.2		c.429G>A	p.Ala143Ala	synonymous	Exon 6 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.756G>A	p.Ala252Ala	synonymous	Exon 6 of 11	ENSP00000262301.12	Q96S06-1
	LMF1	ENST00000963976.1		c.756G>A	p.Ala252Ala	synonymous	Exon 6 of 12	ENSP00000634035.1
	LMF1	ENST00000568897.5	TSL:5	c.105G>A	p.Ala35Ala	synonymous	Exon 5 of 10	ENSP00000458135.1	H3BVI4

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20992 AN: 151884 Hom.: 1703 Cov.: 33

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.0817

Gnomad ASJ AF: 0.0744

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.0661

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.115

GnomAD2 exomes AF: 0.118 AC: 25762 AN: 218024 AF XY: 0.118

Gnomad AFR exome AF: 0.209

Gnomad AMR exome AF: 0.0538

Gnomad ASJ exome AF: 0.0756

Gnomad EAS exome AF: 0.261

Gnomad FIN exome AF: 0.0740

Gnomad NFE exome AF: 0.115

Gnomad OTH exome AF: 0.0975

GnomAD4 exome AF: 0.119 AC: 172443 AN: 1445648 Hom.: 11450 Cov.: 32 AF XY: 0.119 AC XY: 85281 AN XY: 717368

African (AFR) AF: 0.216 AC: 7183 AN: 33248

American (AMR) AF: 0.0571 AC: 2401 AN: 42066

Ashkenazi Jewish (ASJ) AF: 0.0793 AC: 2042 AN: 25744

East Asian (EAS) AF: 0.282 AC: 10971 AN: 38966

South Asian (SAS) AF: 0.122 AC: 10181 AN: 83346

European-Finnish (FIN) AF: 0.0785 AC: 4092 AN: 52124

Middle Eastern (MID) AF: 0.0510 AC: 293 AN: 5748

European-Non Finnish (NFE) AF: 0.116 AC: 128116 AN: 1104568

Other (OTH) AF: 0.120 AC: 7164 AN: 59838

GnomAD4 genome AF: 0.138 AC: 21029 AN: 152002 Hom.: 1709 Cov.: 33 AF XY: 0.136 AC XY: 10074 AN XY: 74290

African (AFR) AF: 0.209 AC: 8661 AN: 41412

American (AMR) AF: 0.0816 AC: 1247 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0744 AC: 258 AN: 3470

East Asian (EAS) AF: 0.273 AC: 1398 AN: 5126

South Asian (SAS) AF: 0.132 AC: 637 AN: 4826

European-Finnish (FIN) AF: 0.0661 AC: 700 AN: 10590

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7718 AN: 67976

Other (OTH) AF: 0.115 AC: 243 AN: 2114

Alfa AF: 0.125 Hom.: 5258

Bravo AF: 0.143

Asia WGS AF: 0.258 AC: 895 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	not specified (2)
-	-	1	Cardiovascular phenotype (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	8.6
DANN	Benign	0.80
PhyloP100		0.69
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: rs2076425; hg19: chr16-929711; COSMIC: COSV51894434; COSMIC: COSV51894434;