8-131999969-G-T

Variant summary

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

The NM_015137.6(EFR3A):c.2158-1790G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 151,938 control chromosomes in the GnomAD database, including 8,918 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 0.33 (8918 hom., cov: 31)
• Consequence: EFR3A NM_015137.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0480

Genes affected

EFR3A (HGNC:28970): (EFR3 homolog A) The protein encoded by this gene is part of a complex that plays a role in maintaining an active pool of phosphatidylinositol 4-kinase (PI4K) at the plasma membrane. This protein is thought to be a peripheral membrane protein that associates with the plasma membrane through palmitoylation. Studies indicate that this gene product plays a role in controlling G protein-coupled receptor (GPCR) activity by affecting receptor phosphorylation. Whole exome sequencing studies have implicated mutations in this gene with autism spectrum disorders. [provided by RefSeq, Apr 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EFR3A	NM_015137.6	c.2158-1790G>T		intron_variant		ENST00000254624.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EFR3A	ENST00000254624.10	c.2158-1790G>T		intron_variant		1	NM_015137.6	P3

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50858 AN: 151820 Hom.: 8908 Cov.: 31

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.335 AC: 50897 AN: 151938 Hom.: 8918 Cov.: 31 AF XY: 0.340 AC XY: 25275 AN XY: 74246

Gnomad4 AFR AF: 0.276

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.611

Gnomad4 SAS AF: 0.482

Gnomad4 FIN AF: 0.378

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.325

Alfa AF: 0.242 Hom.: 804

Bravo AF: 0.327

Asia WGS AF: 0.511 AC: 1777 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	4.1
Dann	Benign	0.64

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: rs1062064; hg19: chr8-133012216;