Variant 8-131946572-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_015137.6(EFR3A):c.305A>G(p.His102Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0028 in 1,607,218 control chromosomes in the GnomAD database, including 153 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 10 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 143 hom. )

Consequence

EFR3A
NM_015137.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.32

Variant links:

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]

EFR3A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003976196).

BP6

Variant 8-131946572-A-G is Benign according to our data. Variant chr8-131946572-A-G is described in ClinVar as [Benign]. Clinvar id is 3046203.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00171 (261/152228) while in subpopulation SAS AF= 0.0526 (254/4826). AF 95% confidence interval is 0.0473. There are 10 homozygotes in gnomad4. There are 192 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EFR3A	NM_015137.6 linkuse as main transcript	c.305A>G	p.His102Arg	missense_variant	4/23	ENST00000254624.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EFR3A	ENST00000254624.10 linkuse as main transcript	c.305A>G	p.His102Arg	missense_variant	4/23	1	NM_015137.6	P3	Q14156-1
EFR3A	ENST00000519656.1 linkuse as main transcript	c.197A>G	p.His66Arg	missense_variant	4/23	1		A1	Q14156-2
EFR3A	ENST00000637848.1 linkuse as main transcript	c.386A>G	p.His129Arg	missense_variant	4/23	5
EFR3A	ENST00000522709.5 linkuse as main transcript	c.197A>G	p.His66Arg	missense_variant	4/6	5

Frequencies

GnomAD3 genomes

AF:

0.00174

AC:

264

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0532

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00601

AC:

1455

AN:

242292

Hom.:

AF XY:

0.00825

AC XY:

1080

AN XY:

130876

show subpopulations

Gnomad AFR exome

AF:

0.0000641

Gnomad AMR exome

AF:

0.0000606

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000561

Gnomad SAS exome

AF:

0.0493

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000637

Gnomad OTH exome

AF:

0.00257

GnomAD4 exome

AF:

0.00291

AC:

4236

AN:

1454990

Hom.:

143

Cov.:

AF XY:

0.00417

AC XY:

3015

AN XY:

723396

show subpopulations

Gnomad4 AFR exome

AF:

0.0000905

Gnomad4 AMR exome

AF:

0.0000684

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000102

Gnomad4 SAS exome

AF:

0.0467

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000478

Gnomad4 OTH exome

AF:

0.00331

GnomAD4 genome

AF:

0.00171

AC:

261

AN:

152228

Hom.:

Cov.:

AF XY:

0.00258

AC XY:

192

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0526

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000337

Hom.:

Bravo

AF:

0.000302

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00677

AC:

821

Asia WGS

AF:

0.0210

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

EFR3A-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 19, 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

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0047

T;.;T;.

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.068

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.75

T;T;T;T

MetaRNN

Benign

0.0040

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.22

N;.;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

0.99

N;N;.;N

REVEL

Benign

0.069

Sift

Benign

0.55

T;T;.;T

Sift4G

Benign

0.39

T;T;.;T

Polyphen

0.0010

B;.;.;.

Vest4

0.29

MVP

0.42

MPC

0.072

ClinPred

0.021

GERP RS

4.3

Varity_R

0.15

gMVP

0.51

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over