rs814628

Positions:

• chr10-88669895-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004190.4(LIPF):​c.481A>G​(p.Thr161Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.171 in 1,611,740 control chromosomes in the GnomAD database, including 25,364 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.14 (1850 hom., cov: 32)
  • Exomes 𝑓: 0.17 (23514 hom.)
• Consequence: LIPF NM_004190.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.87

Genes affected

LIPF (HGNC:6622): (lipase F, gastric type) This gene encodes gastric lipase, an enzyme involved in the digestion of dietary triglycerides in the gastrointestinal tract, and responsible for 30% of fat digestion processes occurring in human. It is secreted by gastric chief cells in the fundic mucosa of the stomach, and it hydrolyzes the ester bonds of triglycerides under acidic pH conditions. The gene is a member of a conserved gene family of lipases that play distinct roles in neutral lipid metabolism. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017985404).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIPF	NM_004190.4	c.481A>G	p.Thr161Ala	missense_variant	5/10	ENST00000238983.9	NP_004181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIPF	ENST00000238983.9	c.481A>G	p.Thr161Ala	missense_variant	5/10	1	NM_004190.4	ENSP00000238983.5
LIPF	ENST00000355843.2	c.412A>G	p.Thr138Ala	missense_variant	6/11	1		ENSP00000348101.3
LIPF	ENST00000394375.7	c.511A>G	p.Thr171Ala	missense_variant	6/11	2		ENSP00000377900.3
LIPF	ENST00000608620.5	c.382A>G	p.Thr128Ala	missense_variant	5/10	2		ENSP00000477140.1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21263 AN: 152148 Hom.: 1848 Cov.: 32

Gnomad AFR AF: 0.0414

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.150

GnomAD3 exomes AF: 0.176 AC: 44186 AN: 250876 Hom.: 4290 AF XY: 0.180 AC XY: 24425 AN XY: 135602

Gnomad AFR exome AF: 0.0394

Gnomad AMR exome AF: 0.160

Gnomad ASJ exome AF: 0.182

Gnomad EAS exome AF: 0.299

Gnomad SAS exome AF: 0.213

Gnomad FIN exome AF: 0.141

Gnomad NFE exome AF: 0.177

Gnomad OTH exome AF: 0.169

GnomAD4 exome AF: 0.174 AC: 254415 AN: 1459474 Hom.: 23514 Cov.: 30 AF XY: 0.176 AC XY: 127864 AN XY: 726074

Gnomad4 AFR exome AF: 0.0342

Gnomad4 AMR exome AF: 0.167

Gnomad4 ASJ exome AF: 0.180

Gnomad4 EAS exome AF: 0.318

Gnomad4 SAS exome AF: 0.207

Gnomad4 FIN exome AF: 0.145

Gnomad4 NFE exome AF: 0.173

Gnomad4 OTH exome AF: 0.174

GnomAD4 genome AF: 0.140 AC: 21260 AN: 152266 Hom.: 1850 Cov.: 32 AF XY: 0.141 AC XY: 10513 AN XY: 74444

Gnomad4 AFR AF: 0.0413

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.307

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.149

Alfa AF: 0.172 Hom.: 5780

Bravo AF: 0.137

TwinsUK AF: 0.178 AC: 659

ALSPAC AF: 0.167 AC: 644

ESP6500AA AF: 0.0452 AC: 199

ESP6500EA AF: 0.176 AC: 1510

ExAC AF: 0.176 AC: 21356

Asia WGS AF: 0.247 AC: 860 AN: 3478

EpiCase AF: 0.169

EpiControl AF: 0.175

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	.;.;T;.
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.73	T;T;T;T
MetaRNN	Benign	0.0018	T;T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Pathogenic	3.4	.;.;M;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-4.8	D;.;D;.
REVEL	Uncertain	0.46
Sift	Uncertain	0.0070	D;.;D;.
Sift4G	Uncertain	0.0020	D;D;D;D
Polyphen		0.99	.;.;D;.
Vest4		0.28
MPC		0.55
ClinPred		0.025	T
GERP RS		5.2
Varity_R		0.67
gMVP		0.85

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

Publications

LitVar

Other links and lift over

dbSNP: rs814628; hg19: chr10-90429652; COSMIC: COSV53284201; COSMIC: COSV53284201;