Genetic Variant ELF1:p.Asn58Ser (chr13-40958916-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_172373.4(ELF1):c.173A>G(p.Asn58Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.645 in 1,613,070 control chromosomes in the GnomAD database, including 348,751 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.54 ( 25721 hom., cov: 31)

Exomes 𝑓: 0.66 ( 323030 hom. )

Consequence

ELF1
NM_172373.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0450

Variant links:

Genes affected

ELF1 (HGNC:3316): (E74 like ETS transcription factor 1) This gene encodes an E26 transformation-specific related transcription factor. The encoded protein is primarily expressed in lymphoid cells and acts as both an enhancer and a repressor to regulate transcription of various genes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2009]

ELF1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.8838622E-6).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELF1	NM_172373.4 link	c.173A>G	p.Asn58Ser	missense_variant	Exon 3 of 9	ENST00000239882.7	NP_758961.1	P32519-1A0A024RDU6Q6MZZ4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ELF1	ENST00000239882.7 link	c.173A>G	p.Asn58Ser	missense_variant	Exon 3 of 9	1	NM_172373.4	ENSP00000239882.3	P32519-1
ELF1	ENST00000635415.1 link	c.173A>G	p.Asn58Ser	missense_variant	Exon 3 of 9	5		ENSP00000489586.1	A0A0U1RRL5
ELF1	ENST00000625359.1 link	c.173A>G	p.Asn58Ser	missense_variant	Exon 2 of 8	2		ENSP00000486912.1	P32519-2
ELF1	ENST00000498824.4 link	n.173A>G		non_coding_transcript_exon_variant	Exon 2 of 9	2		ENSP00000487240.1	A0A0D9SG85

Frequencies

GnomAD3 genomes

AF:

0.545

AC:

82762

AN:

151838

Hom.:

25729

Cov.:

show subpopulations

Gnomad AFR

AF:

0.254

Gnomad AMI

AF:

0.788

Gnomad AMR

AF:

0.655

Gnomad ASJ

AF:

0.639

Gnomad EAS

AF:

0.182

Gnomad SAS

AF:

0.571

Gnomad FIN

AF:

0.715

Gnomad MID

AF:

0.656

Gnomad NFE

AF:

0.687

Gnomad OTH

AF:

0.581

GnomAD3 exomes

AF:

0.614

AC:

154113

AN:

250868

Hom.:

50931

AF XY:

0.624

AC XY:

84564

AN XY:

135622

show subpopulations

Gnomad AFR exome

AF:

0.246

Gnomad AMR exome

AF:

0.694

Gnomad ASJ exome

AF:

0.644

Gnomad EAS exome

AF:

0.185

Gnomad SAS exome

AF:

0.594

Gnomad FIN exome

AF:

0.706

Gnomad NFE exome

AF:

0.696

Gnomad OTH exome

AF:

0.637

GnomAD4 exome

AF:

0.656

AC:

957817

AN:

1461114

Hom.:

323030

Cov.:

AF XY:

0.655

AC XY:

476350

AN XY:

726868

show subpopulations

Gnomad4 AFR exome

AF:

0.249

Gnomad4 AMR exome

AF:

0.692

Gnomad4 ASJ exome

AF:

0.639

Gnomad4 EAS exome

AF:

0.192

Gnomad4 SAS exome

AF:

0.593

Gnomad4 FIN exome

AF:

0.702

Gnomad4 NFE exome

AF:

0.688

Gnomad4 OTH exome

AF:

0.610

GnomAD4 genome

AF:

0.545

AC:

82756

AN:

151956

Hom.:

25721

Cov.:

AF XY:

0.549

AC XY:

40740

AN XY:

74242

show subpopulations

Gnomad4 AFR

AF:

0.254

Gnomad4 AMR

AF:

0.654

Gnomad4 ASJ

AF:

0.639

Gnomad4 EAS

AF:

0.183

Gnomad4 SAS

AF:

0.570

Gnomad4 FIN

AF:

0.715

Gnomad4 NFE

AF:

0.687

Gnomad4 OTH

AF:

0.573

Alfa

AF:

0.656

Hom.:

87437

Bravo

AF:

0.530

TwinsUK

AF:

0.679

AC:

2518

ALSPAC

AF:

0.679

AC:

2618

ESP6500AA

AF:

0.257

AC:

1133

ESP6500EA

AF:

0.690

AC:

5931

ExAC

AF:

0.608

AC:

73757

Asia WGS

AF:

0.339

AC:

1178

AN:

3478

EpiCase

AF:

0.694

EpiControl

AF:

0.698

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.10

T;.;T

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.85

D;D;D

MetaRNN

Benign

0.0000029

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;L;.

PrimateAI

Benign

0.40

PROVEAN

Benign

-2.0

N;.;.

REVEL

Benign

0.068

Sift

Benign

0.17

T;.;.

Sift4G

Benign

0.27

T;T;.

Polyphen

0.015

B;.;.

Vest4

0.037

MPC

0.13

ClinPred

0.0055

GERP RS

0.35

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.038

gMVP

0.22

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over