Variant chr19-42248547-C-G 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_006494.4(ERF):c.1565G>C(p.Gly522Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000286 in 1,400,744 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

ERF
NM_006494.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.66

Variant links:

Genes affected

ERF (HGNC:3444): (ETS2 repressor factor) ETS2 is a transcription factor and protooncogene involved in development, apoptosis, and the regulation of telomerase. The protein encoded by this gene binds to the ETS2 promoter and is a strong repressor of ETS2 transcription. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Aug 2015]

ERF 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=0.14433596).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERF	NM_006494.4 linkuse as main transcript	c.1565G>C	p.Gly522Ala	missense_variant	4/4	ENST00000222329.9	NP_006485.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERF	ENST00000222329.9 linkuse as main transcript	c.1565G>C	p.Gly522Ala	missense_variant	4/4	1	NM_006494.4	ENSP00000222329	P1	P50548-1
ERF	ENST00000440177.6 linkuse as main transcript	c.1340G>C	p.Gly447Ala	missense_variant	4/4	2		ENSP00000388173		P50548-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000286

AC:

AN:

1400744

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

691774

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000369

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 20, 2023

The c.1565G>C (p.G522A) alteration is located in exon 4 (coding exon 4) of the ERF gene. This alteration results from a G to C substitution at nucleotide position 1565, causing the glycine (G) at amino acid position 522 to be replaced by an alanine (A). 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

Benign

0.065

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.11

T;.

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.072

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

N;.

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.61

N;N

REVEL

Benign

0.058

Sift

Benign

0.23

T;T

Sift4G

Benign

0.31

T;T

Polyphen

0.46

P;.

Vest4

0.17

MutPred

0.14

Loss of relative solvent accessibility (P = 0.0071);.;

MVP

0.48

MPC

0.68

ClinPred

0.19

GERP RS

3.9

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.8

Varity_R

0.070

gMVP

0.11

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