rs13334376

Positions:

• chr16-971001-C-A
• chr16-971001-C-G
• chr16-971001-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001352019.2(LMF1):​c.-135+10144G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00075 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0075 (164 hom.)
• Consequence: LMF1 NM_001352019.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.00

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 16-971001-C-A is Benign according to our data. Variant chr16-971001-C-A is described in ClinVar as [Benign]. Clinvar id is 1242679.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000749 (40/53398) while in subpopulation AFR AF= 0.00223 (17/7620). AF 95% confidence interval is 0.00142. There are 0 homozygotes in gnomad4. There are 18 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 164 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMF1	NM_022773.4			upstream_gene_variant		ENST00000262301.16	NP_073610.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMF1	ENST00000262301.16			upstream_gene_variant		5	NM_022773.4	ENSP00000262301	P1

Frequencies

GnomAD3 genomes AF: 0.000749 AC: 40 AN: 53384 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00223

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000742

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000744

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000619

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0761 AC: 5608 AN: 73662 Hom.: 237 AF XY: 0.0733 AC XY: 3065 AN XY: 41818

Gnomad AFR exome AF: 0.114

Gnomad AMR exome AF: 0.0599

Gnomad ASJ exome AF: 0.0417

Gnomad EAS exome AF: 0.0281

Gnomad SAS exome AF: 0.0601

Gnomad FIN exome AF: 0.0791

Gnomad NFE exome AF: 0.0874

Gnomad OTH exome AF: 0.0715

GnomAD4 exome AF: 0.00750 AC: 4387 AN: 585148 Hom.: 164 Cov.: 0 AF XY: 0.00838 AC XY: 2392 AN XY: 285380

Gnomad4 AFR exome AF: 0.0325

Gnomad4 AMR exome AF: 0.0459

Gnomad4 ASJ exome AF: 0.00477

Gnomad4 EAS exome AF: 0.00624

Gnomad4 SAS exome AF: 0.0136

Gnomad4 FIN exome AF: 0.0215

Gnomad4 NFE exome AF: 0.00559

Gnomad4 OTH exome AF: 0.00816

GnomAD4 genome AF: 0.000749 AC: 40 AN: 53398 Hom.: 0 Cov.: 0 AF XY: 0.000680 AC XY: 18 AN XY: 26458

Gnomad4 AFR AF: 0.00223

Gnomad4 AMR AF: 0.000742

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000742

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000619

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	3.5
DANN	Benign	0.32

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs13334376; hg19: chr16-1021001;