rs7187700

Variant names:

• chr16-962750-G-A
• rs7187700
• NM_022773.4:c.193+8038C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022773.4(LMF1):​c.193+8038C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 152,136 control chromosomes in the GnomAD database, including 7,368 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (7368 hom., cov: 32)
• Consequence: LMF1 NM_022773.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.714
• Publications: 11 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: Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMF1	NM_022773.4	c.193+8038C>T		intron_variant	Intron 1 of 10	ENST00000262301.16	NP_073610.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMF1	ENST00000262301.16	c.193+8038C>T		intron_variant	Intron 1 of 10	5	NM_022773.4	ENSP00000262301.12

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44104 AN: 152018 Hom.: 7353 Cov.: 32

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.0960

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.265

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.290 AC: 44161 AN: 152136 Hom.: 7368 Cov.: 32 AF XY: 0.288 AC XY: 21433 AN XY: 74378

African (AFR) AF: 0.466 AC: 19341 AN: 41482

American (AMR) AF: 0.223 AC: 3402 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 587 AN: 3472

East Asian (EAS) AF: 0.0951 AC: 493 AN: 5186

South Asian (SAS) AF: 0.282 AC: 1357 AN: 4814

European-Finnish (FIN) AF: 0.247 AC: 2614 AN: 10592

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.230 AC: 15649 AN: 67990

Other (OTH) AF: 0.264 AC: 558 AN: 2112

Alfa AF: 0.248 Hom.: 19439

Bravo AF: 0.294

Asia WGS AF: 0.244 AC: 851 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.0
DANN	Benign	0.63
PhyloP100		0.71
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: rs7187700; hg19: chr16-1012750;