Genetic Variant EFR3A:c.489-6_489-5delTT (chr8-131953798-CTT-C) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1

The NM_015137.6(EFR3A):c.489-6_489-5delTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0223 in 1,323,574 control chromosomes in the GnomAD database, including 222 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.039 ( 191 hom., cov: 30)

Exomes 𝑓: 0.020 ( 31 hom. )

Consequence

EFR3A
NM_015137.6 splice_region, intron

Scores

Not classified

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.536

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 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 no_assertion_criteria_provided, 0 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 rank	MANE	Protein	UniProt
EFR3A	NM_015137.6 link	c.489-6_489-5delTT		splice_region_variant, intron_variant	Intron 5 of 22	ENST00000254624.10	NP_055952.2	Q14156-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
EFR3A	ENST00000254624.10 link	c.489-19_489-18delTT	intron_variant	Intron 5 of 22	1	NM_015137.6	ENSP00000254624.5	Q14156-1
EFR3A	ENST00000519656.1 link	c.381-19_381-18delTT	intron_variant	Intron 5 of 22	1		ENSP00000428086.1	Q14156-2
EFR3A	ENST00000637848.1 link	c.570-19_570-18delTT	intron_variant	Intron 5 of 22	5		ENSP00000490312.1	A0A1B0GUZ7
EFR3A	ENST00000522709.5 link	c.381-19_381-18delTT	intron_variant	Intron 5 of 5	5		ENSP00000430512.1	E5RJS1

Frequencies

GnomAD3 genomes

AF:

0.0391

AC:

5428

AN:

138656

Hom.:

192

Cov.:

show subpopulations

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.:

AF XY:

0.0401

AC XY:

1167

AN XY:

29072

show subpopulations

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.:

AF XY:

0.0201

AC XY:

11675

AN XY:

579962

show subpopulations

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.:

AF XY:

0.0390

AC XY:

2616

AN XY:

67082

show subpopulations

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: no assertion criteria provided

LINK: link

Submissions by phenotype

EFR3A-related disorder

Benign:1

May 03, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

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