rs17493811

Positions:

• chr6-32177622-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_032741.5(AGPAT1):​c.-10+379G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0188 in 152,254 control chromosomes in the GnomAD database, including 40 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 0.019 (40 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AGPAT1 NM_032741.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.87

Genes affected

AGPAT1 (HGNC:324): (1-acylglycerol-3-phosphate O-acyltransferase 1) This gene encodes an enzyme that converts lysophosphatidic acid (LPA) into phosphatidic acid (PA). LPA and PA are two phospholipids involved in signal transduction and in lipid biosynthesis in cells. This enzyme localizes to the endoplasmic reticulum. This gene is located in the class III region of the human major histocompatibility complex. Alternative splicing results in two transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0188 (2856/152254) while in subpopulation NFE AF= 0.0285 (1938/68022). AF 95% confidence interval is 0.0274. There are 40 homozygotes in gnomad4. There are 1390 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 40 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGPAT1	NM_032741.5	c.-10+379G>C		intron_variant			NP_116130.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGPAT1	ENST00000336984.6	c.-10+379G>C		intron_variant		1		ENSP00000337463.6
AGPAT1	ENST00000395497.5	c.-88G>C		5_prime_UTR_variant	1/7	5		ENSP00000378875.1

Frequencies

GnomAD3 genomes AF: 0.0188 AC: 2856 AN: 152136 Hom.: 40 Cov.: 32

Gnomad AFR AF: 0.00476

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0168

Gnomad ASJ AF: 0.00662

Gnomad EAS AF: 0.0120

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.0267

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0285

Gnomad OTH AF: 0.0178

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 90 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 54

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0188 AC: 2856 AN: 152254 Hom.: 40 Cov.: 32 AF XY: 0.0187 AC XY: 1390 AN XY: 74440

Gnomad4 AFR AF: 0.00474

Gnomad4 AMR AF: 0.0167

Gnomad4 ASJ AF: 0.00662

Gnomad4 EAS AF: 0.0120

Gnomad4 SAS AF: 0.0112

Gnomad4 FIN AF: 0.0267

Gnomad4 NFE AF: 0.0285

Gnomad4 OTH AF: 0.0176

Alfa AF: 0.0256 Hom.: 13

Bravo AF: 0.0168

Asia WGS AF: 0.0100 AC: 36 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	16
DANN	Benign	0.85

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17493811; hg19: chr6-32145399;