rs150957667

Variant names:

• chr16-931754-T-C
• rs150957667
• NM_022773.4:c.514+2490A>G

Your query was ambiguous. Multiple possible variants found:

• chr16-931754-T-C
• chr16-931754-T-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001352017.2(LMF1):​c.-250A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00783 in 1,287,196 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0059 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0081 (41 hom.)
• Consequence: LMF1 NM_001352017.2 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.560
• Publications: 0 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-AS1 (HGNC:50469): (LMF1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 16-931754-T-C is Benign according to our data. Variant chr16-931754-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3895390.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00593 (903/152302) while in subpopulation AMR AF = 0.00889 (136/15298). AF 95% confidence interval is 0.00819. There are 2 homozygotes in GnomAd4. There are 416 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001352017.2. 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.514+2490A>G		intron	N/A	NP_073610.2	Q96S06-1
	LMF1	NM_001352017.2		c.-250A>G		5_prime_UTR	Exon 4 of 12	NP_001338946.1	H3BVI4
	LMF1	NM_001352020.1		c.514+2490A>G		intron	N/A	NP_001338949.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMF1	ENST00000262301.16	TSL:5 MANE Select	c.514+2490A>G		intron	N/A	ENSP00000262301.12	Q96S06-1
	LMF1	ENST00000963976.1		c.514+2490A>G		intron	N/A	ENSP00000634035.1
	LMF1	ENST00000568897.5	TSL:5	c.-137-20675A>G		intron	N/A	ENSP00000458135.1	H3BVI4

Frequencies

GnomAD3 genomes AF: 0.00595 AC: 905 AN: 152184 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00164

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00897

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00207

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00878

Gnomad OTH AF: 0.00956

GnomAD2 exomes AF: 0.00654 AC: 838 AN: 128064 AF XY: 0.00646

Gnomad AFR exome AF: 0.000985

Gnomad AMR exome AF: 0.00780

Gnomad ASJ exome AF: 0.0124

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00241

Gnomad NFE exome AF: 0.00978

Gnomad OTH exome AF: 0.0110

GnomAD4 exome AF: 0.00808 AC: 9172 AN: 1134894 Hom.: 41 Cov.: 31 AF XY: 0.00780 AC XY: 4344 AN XY: 556700

African (AFR) AF: 0.00111 AC: 27 AN: 24340

American (AMR) AF: 0.00800 AC: 226 AN: 28258

Ashkenazi Jewish (ASJ) AF: 0.0112 AC: 178 AN: 15936

East Asian (EAS) AF: 0.00 AC: 0 AN: 12838

South Asian (SAS) AF: 0.00112 AC: 85 AN: 76110

European-Finnish (FIN) AF: 0.00253 AC: 32 AN: 12656

Middle Eastern (MID) AF: 0.0112 AC: 31 AN: 2770

European-Non Finnish (NFE) AF: 0.00893 AC: 8218 AN: 920648

Other (OTH) AF: 0.00907 AC: 375 AN: 41338

GnomAD4 genome AF: 0.00593 AC: 903 AN: 152302 Hom.: 2 Cov.: 33 AF XY: 0.00559 AC XY: 416 AN XY: 74476

African (AFR) AF: 0.00164 AC: 68 AN: 41560

American (AMR) AF: 0.00889 AC: 136 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0138 AC: 48 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4824

European-Finnish (FIN) AF: 0.00207 AC: 22 AN: 10620

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00878 AC: 597 AN: 68022

Other (OTH) AF: 0.00946 AC: 20 AN: 2114

Alfa AF: 0.00838 Hom.: 2

Bravo AF: 0.00667

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.60
DANN	Benign	0.16
PhyloP100		-0.56
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs150957667; hg19: chr16-981754;