10-88665570-T-C

Variant names:

• chr10-88665570-T-C
• rs814624
• NM_004190.4:c.-12+1079T>C

Variant summary

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

The NM_004190.4(LIPF):​c.-12+1079T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.267 in 1,528,326 control chromosomes in the GnomAD database, including 56,114 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 0.27 (5760 hom., cov: 31)
  • Exomes 𝑓: 0.27 (50354 hom.)
• Consequence: LIPF NM_004190.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0880
• Publications: 7 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LIPF	NM_004190.4	c.-12+1079T>C		intron_variant	Intron 1 of 9	ENST00000238983.9	NP_004181.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LIPF	ENST00000238983.9	c.-12+1079T>C		intron_variant	Intron 1 of 9	1	NM_004190.4	ENSP00000238983.5

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41416 AN: 151852 Hom.: 5746 Cov.: 31

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.299

GnomAD2 exomes AF: 0.293 AC: 39391 AN: 134440 AF XY: 0.293

Gnomad AFR exome AF: 0.254

Gnomad AMR exome AF: 0.311

Gnomad ASJ exome AF: 0.344

Gnomad EAS exome AF: 0.368

Gnomad FIN exome AF: 0.255

Gnomad NFE exome AF: 0.264

Gnomad OTH exome AF: 0.299

GnomAD4 exome AF: 0.266 AC: 366752 AN: 1376356 Hom.: 50354 Cov.: 29 AF XY: 0.268 AC XY: 182334 AN XY: 679524

African (AFR) AF: 0.261 AC: 8201 AN: 31458

American (AMR) AF: 0.318 AC: 11361 AN: 35680

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 8600 AN: 25116

East Asian (EAS) AF: 0.393 AC: 14022 AN: 35676

South Asian (SAS) AF: 0.302 AC: 23878 AN: 79064

European-Finnish (FIN) AF: 0.258 AC: 8729 AN: 33870

Middle Eastern (MID) AF: 0.336 AC: 1903 AN: 5668

European-Non Finnish (NFE) AF: 0.255 AC: 273462 AN: 1072208

Other (OTH) AF: 0.288 AC: 16596 AN: 57616

GnomAD4 genome AF: 0.273 AC: 41465 AN: 151970 Hom.: 5760 Cov.: 31 AF XY: 0.274 AC XY: 20348 AN XY: 74278

African (AFR) AF: 0.259 AC: 10742 AN: 41454

American (AMR) AF: 0.327 AC: 4980 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1201 AN: 3472

East Asian (EAS) AF: 0.381 AC: 1968 AN: 5168

South Asian (SAS) AF: 0.317 AC: 1523 AN: 4806

European-Finnish (FIN) AF: 0.237 AC: 2501 AN: 10568

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.259 AC: 17614 AN: 67952

Other (OTH) AF: 0.300 AC: 631 AN: 2102

Alfa AF: 0.257 Hom.: 2611

Bravo AF: 0.277

Asia WGS AF: 0.348 AC: 1211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.6
DANN	Benign	0.70
PhyloP100		-0.088
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: rs814624; hg19: chr10-90425327; COSMIC: COSV53286009;