8-131953798-CTT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_015137.6(EFR3A):c.489-6_489-5del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0223 in 1,323,574 control chromosomes in the GnomAD database, including 222 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.039 (191 hom., cov: 30)
  • Exomes 𝑓: 0.020 (31 hom.)
• Consequence: EFR3A NM_015137.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.536

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 -10 ACMG points.

• BP6: Variant 8-131953798-CTT-C is Benign according to our data. Variant chr8-131953798-CTT-C is described in ClinVar as [Benign]. Clinvar id is 3059061.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0988 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EFR3A	NM_015137.6	c.489-6_489-5del		intron_variant		ENST00000254624.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EFR3A	ENST00000254624.10	c.489-6_489-5del		intron_variant		1	NM_015137.6	P3
EFR3A	ENST00000519656.1	c.381-6_381-5del		intron_variant		1		A1
EFR3A	ENST00000522709.5	c.381-6_381-5del		intron_variant		5
EFR3A	ENST00000637848.1	c.570-6_570-5del		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0391 AC: 5428 AN: 138656 Hom.: 192 Cov.: 30

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0306

Gnomad ASJ AF: 0.0216

Gnomad EAS AF: 0.000205

Gnomad SAS AF: 0.00318

Gnomad FIN AF: 0.0116

Gnomad MID AF: 0.0483

Gnomad NFE AF: 0.0138

Gnomad OTH AF: 0.0356

GnomAD3 exomes AF: 0.0422 AC: 2320 AN: 55024 Hom.: 5 AF XY: 0.0401 AC XY: 1167 AN XY: 29072

Gnomad AFR exome AF: 0.125

Gnomad AMR exome AF: 0.0473

Gnomad ASJ exome AF: 0.0486

Gnomad EAS exome AF: 0.0158

Gnomad SAS exome AF: 0.0304

Gnomad FIN exome AF: 0.0306

Gnomad NFE exome AF: 0.0364

Gnomad OTH exome AF: 0.0496

GnomAD4 exome AF: 0.0203 AC: 24045 AN: 1184938 Hom.: 31 AF XY: 0.0201 AC XY: 11675 AN XY: 579962

Gnomad4 AFR exome AF: 0.103

Gnomad4 AMR exome AF: 0.0314

Gnomad4 ASJ exome AF: 0.0283

Gnomad4 EAS exome AF: 0.00527

Gnomad4 SAS exome AF: 0.0177

Gnomad4 FIN exome AF: 0.0156

Gnomad4 NFE exome AF: 0.0179

Gnomad4 OTH exome AF: 0.0289

GnomAD4 genome AF: 0.0391 AC: 5420 AN: 138636 Hom.: 191 Cov.: 30 AF XY: 0.0390 AC XY: 2616 AN XY: 67082

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.0305

Gnomad4 ASJ AF: 0.0216

Gnomad4 EAS AF: 0.000206

Gnomad4 SAS AF: 0.00297

Gnomad4 FIN AF: 0.0116

Gnomad4 NFE AF: 0.0138

Gnomad4 OTH AF: 0.0355

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

EFR3A-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 03, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

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: rs112472883; hg19: chr8-132966045;