Variant 1-202012678-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_004433.5(ELF3):c.517G>A(p.Gly173Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000336 in 1,609,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

ELF3
NM_004433.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.70

Variant links:

Genes affected

ELF3 (HGNC:3318): (E74 like ETS transcription factor 3) Enables DNA-binding transcription activator activity, RNA polymerase II-specific and sequence-specific double-stranded DNA binding activity. Involved in inflammatory response; negative regulation of transcription, DNA-templated; and positive regulation of transcription by RNA polymerase II. Located in Golgi apparatus; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ELF3 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01646918).

BP6

Variant 1-202012678-G-A is Benign according to our data. Variant chr1-202012678-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2386681.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAdExome4 at 51 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ELF3	NM_004433.5 linkuse as main transcript	c.517G>A	p.Gly173Ser	missense_variant	5/9	ENST00000367284.10	NP_004424.3
ELF3	NM_001114309.2 linkuse as main transcript	c.517G>A	p.Gly173Ser	missense_variant	5/9		NP_001107781.1
ELF3	XM_005244942.4 linkuse as main transcript	c.517G>A	p.Gly173Ser	missense_variant	5/6		XP_005244999.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELF3	ENST00000367284.10 linkuse as main transcript	c.517G>A	p.Gly173Ser	missense_variant	5/9	1	NM_004433.5	ENSP00000356253	P1	P78545-1
	ENST00000504773.1 linkuse as main transcript	n.215+1094G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000493

AC:

AN:

243260

Hom.:

AF XY:

0.0000378

AC XY:

AN XY:

132182

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000176

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:

0.0000460

Gnomad OTH exome

AF:

0.000167

GnomAD4 exome

AF:

0.0000350

AC:

AN:

1456910

Hom.:

Cov.:

AF XY:

0.0000386

AC XY:

AN XY:

724506

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000181

Gnomad4 ASJ exome

AF:

0.0000772

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000324

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000400

Hom.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000659

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 30, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.010

DANN

Benign

0.58

DEOGEN2

Benign

0.092

T;T;T;T

Eigen

Benign

-2.4

Eigen_PC

Benign

-2.6

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.43

.;.;T;T

M_CAP

Benign

0.0057

MetaRNN

Benign

0.016

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.060

N;N;N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

0.86

N;N;N;N

REVEL

Benign

0.048

Sift

Benign

0.66

T;T;T;T

Sift4G

Benign

0.55

T;T;T;T

Polyphen

0.0010

B;B;B;.

Vest4

0.035

MVP

0.43

MPC

0.28

ClinPred

0.019

GERP RS

-10

Varity_R

0.027

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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