8-41612000-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_178819.4(GPAT4):c.701+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00146 in 1,613,684 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (30 hom.)
• Consequence: GPAT4 NM_178819.4 splice_region, intron
• Scores: Splicing: ADA: 0.00002120
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.64

Genes affected

GPAT4 (HGNC:20880): (glycerol-3-phosphate acyltransferase 4) Lysophosphatidic acid acyltransferases (EC 2.3.1.51) catalyze the conversion of lysophosphatidic acid (LPA) to phosphatidic acid (PA). LPA and PA are involved in signal transduction and lipid biosynthesis.[supplied by OMIM, Apr 2004]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 8-41612000-C-T is Benign according to our data. Variant chr8-41612000-C-T is described in ClinVar as [Benign]. Clinvar id is 725885.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00135 (206/152258) while in subpopulation SAS AF= 0.0286 (138/4822). AF 95% confidence interval is 0.0247. There are 3 homozygotes in gnomad4. There are 134 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPAT4	NM_178819.4	c.701+8C>T		splice_region_variant, intron_variant		ENST00000396987.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPAT4	ENST00000396987.7	c.701+8C>T		splice_region_variant, intron_variant		1	NM_178819.4	P1
	ENST00000581909.1	n.547-2126G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00135 AC: 205 AN: 152140 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00321

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0284

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00292 AC: 733 AN: 250834 Hom.: 8 AF XY: 0.00376 AC XY: 510 AN XY: 135596

Gnomad AFR exome AF: 0.000617

Gnomad AMR exome AF: 0.000261

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0229

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00147 AC: 2146 AN: 1461426 Hom.: 30 Cov.: 31 AF XY: 0.00204 AC XY: 1482 AN XY: 727028

Gnomad4 AFR exome AF: 0.000508

Gnomad4 AMR exome AF: 0.000626

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.0227

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.0000207

Gnomad4 OTH exome AF: 0.00182

GnomAD4 genome AF: 0.00135 AC: 206 AN: 152258 Hom.: 3 Cov.: 33 AF XY: 0.00180 AC XY: 134 AN XY: 74448

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.00320

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0286

Gnomad4 FIN AF: 0.000189

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.000326 Hom.: 1

Bravo AF: 0.00108

Asia WGS AF: 0.00866 AC: 30 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 15, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.066
Dann	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000021
dbscSNV1_RF	Benign	0.0
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: rs138755218; hg19: chr8-41469519;