Variant 13-40933853-T-C 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_172373.4(ELF1):c.1432A>G(p.Thr478Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

ELF1
NM_172373.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.12

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 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=0.20718032).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ELF1	NM_172373.4 linkuse as main transcript	c.1432A>G	p.Thr478Ala	missense_variant	9/9	ENST00000239882.7	NP_758961.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ELF1	ENST00000239882.7 linkuse as main transcript	c.1432A>G	p.Thr478Ala	missense_variant	9/9	1	NM_172373.4	ENSP00000239882	P1	P32519-1
ELF1	ENST00000635415.1 linkuse as main transcript	c.1432A>G	p.Thr478Ala	missense_variant	9/9	5		ENSP00000489586
ELF1	ENST00000625359.1 linkuse as main transcript	c.1360A>G	p.Thr454Ala	missense_variant	8/8	2		ENSP00000486912		P32519-2
ELF1	ENST00000498824.4 linkuse as main transcript	c.*1175A>G		3_prime_UTR_variant, NMD_transcript_variant	9/9	2		ENSP00000487240

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251478

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135910

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:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727246

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:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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

Apr 09, 2024

The c.1432A>G (p.T478A) alteration is located in exon 9 (coding exon 8) of the ELF1 gene. This alteration results from a A to G substitution at nucleotide position 1432, causing the threonine (T) at amino acid position 478 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

0.085

BayesDel_addAF

Benign

-0.073

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

T;.;T

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.78

T;T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.21

T;T;T

MetaSVM

Benign

-0.71

MutationAssessor

Uncertain

2.0

M;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.5

N;.;.

REVEL

Benign

0.095

Sift

Uncertain

0.026

D;.;.

Sift4G

Benign

0.082

T;T;.

Polyphen

1.0

D;.;.

Vest4

0.33

MutPred

0.21

Gain of catalytic residue at M477 (P = 0.0021);.;Gain of catalytic residue at M477 (P = 0.0021);

MVP

0.53

MPC

0.68

ClinPred

0.61

GERP RS

5.4

Varity_R

0.13

gMVP

0.67

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