6-161223508-C-T

Variant names:

• chr6-161223508-C-T
• rs3778229
• NM_020133.3:c.178+8528G>A

Variant summary

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

The NM_020133.3(AGPAT4):​c.178+8528G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 152,000 control chromosomes in the GnomAD database, including 10,789 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 0.37 (10789 hom., cov: 32)
• Consequence: AGPAT4 NM_020133.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 3 publications found

Genes affected

AGPAT4 (HGNC:20885): (1-acylglycerol-3-phosphate O-acyltransferase 4) This gene encodes a member of the 1-acylglycerol-3-phosphate O-acyltransferase family. This integral membrane protein converts lysophosphatidic acid to phosphatidic acid, the second step in de novo phospholipid biosynthesis. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020133.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGPAT4	NM_020133.3	MANE Select	c.178+8528G>A		intron	N/A	NP_064518.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGPAT4	ENST00000320285.9	TSL:1 MANE Select	c.178+8528G>A		intron	N/A	ENSP00000314036.4
	AGPAT4	ENST00000366911.9	TSL:1	c.178+8528G>A		intron	N/A	ENSP00000355878.5
	AGPAT4	ENST00000436279.1	TSL:1	n.178+8528G>A		intron	N/A	ENSP00000413901.1

Frequencies

GnomAD3 genomes AF: 0.368 AC: 55933 AN: 151882 Hom.: 10791 Cov.: 32

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.286

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.350

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.368 AC: 55941 AN: 152000 Hom.: 10789 Cov.: 32 AF XY: 0.362 AC XY: 26900 AN XY: 74300

African (AFR) AF: 0.290 AC: 12017 AN: 41452

American (AMR) AF: 0.305 AC: 4651 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1436 AN: 3472

East Asian (EAS) AF: 0.329 AC: 1697 AN: 5162

South Asian (SAS) AF: 0.338 AC: 1629 AN: 4818

European-Finnish (FIN) AF: 0.340 AC: 3588 AN: 10546

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.439 AC: 29849 AN: 67962

Other (OTH) AF: 0.345 AC: 730 AN: 2114

Alfa AF: 0.413 Hom.: 22460

Bravo AF: 0.363

Asia WGS AF: 0.303 AC: 1051 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.27
DANN	Benign	0.64
PhyloP100		-1.1
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: rs3778229; hg19: chr6-161644540; COSMIC: COSV57244311;