Variant chr2-25091399-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014971.2(EFR3B):c.82G>A(p.Glu28Lys) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000358 in 1,396,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000036 ( 0 hom. )

Consequence

EFR3B
NM_014971.2 missense, splice_region

Scores

Splicing: ADA: 0.0008013

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.15

Variant links:

Genes affected

EFR3B (HGNC:29155): (EFR3 homolog B) Involved in phosphatidylinositol phosphate biosynthetic process and protein localization to plasma membrane. Located in actin cytoskeleton; cytosol; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

EFR3B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16205621).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EFR3B	NM_014971.2 link	c.82G>A	p.Glu28Lys	missense_variant, splice_region_variant	2/23	ENST00000403714.8	NP_055786.1	Q9Y2G0-1B3KT90
EFR3B	NM_001319099.2 link	c.-24G>A		splice_region_variant	2/23		NP_001306028.1	E7ESK9B3KT90
EFR3B	NM_001319099.2 link	c.-24G>A		5_prime_UTR_variant	2/23		NP_001306028.1	E7ESK9B3KT90

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
EFR3B	ENST00000403714.8 link	c.82G>A	p.Glu28Lys	missense_variant, splice_region_variant	2/23	5	NM_014971.2	ENSP00000384081.3	Q9Y2G0-1
EFR3B	ENST00000402191.5 link	c.-24G>A		splice_region_variant	2/23	5		ENSP00000385832.1	E7ESK9
EFR3B	ENST00000401432.7 link	c.82G>A	p.Glu28Lys	missense_variant, splice_region_variant	2/19	2		ENSP00000386082.3	Q9Y2G0-3
EFR3B	ENST00000402191 link	c.-24G>A		5_prime_UTR_variant	2/23	5		ENSP00000385832.1	E7ESK9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000661

AC:

AN:

151198

Hom.:

AF XY:

0.0000124

AC XY:

AN XY:

80404

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000170

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000358

AC:

AN:

1396882

Hom.:

Cov.:

AF XY:

0.00000581

AC XY:

AN XY:

689048

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000127

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000371

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 02, 2024

The c.82G>A (p.E28K) alteration is located in exon 2 (coding exon 2) of the EFR3B gene. This alteration results from a G to A substitution at nucleotide position 82, causing the glutamic acid (E) at amino acid position 28 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.46

BayesDel_addAF

Benign

0.0081

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.027

.;T

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.86

D;T

M_CAP

Benign

0.044

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-0.68

MutationAssessor

Benign

1.3

L;L

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.15

Sift

Benign

0.54

T;T

Sift4G

Benign

0.38

T;T

Polyphen

0.17

B;D

Vest4

0.33

MutPred

0.41

Gain of ubiquitination at E28 (P = 0.0117);Gain of ubiquitination at E28 (P = 0.0117);

MVP

0.19

ClinPred

0.88

GERP RS

4.2

Varity_R

0.22

gMVP

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00080

dbscSNV1_RF

Benign

0.050

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