chr4-139137692-C-T

Variant names:

• chr4-139137692-C-T
• rs747574524
• NM_001331036.3:c.10G>A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PP5_Moderate BP4 BS2

The NM_001331036.3(ELF2):​c.10G>A​(p.Ala4Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000226 in 1,461,666 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 Likely pathogenic (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: ELF2 NM_001331036.3 missense
• Clinical Significance: Likely pathogenic criteria provided, single submitter P:1 U:1
• Conservation: PhyloP100: 4.58

Genes affected

ELF2 (HGNC:3317): (E74 like ETS transcription factor 2) Enables DNA-binding transcription factor activity, RNA polymerase II-specific and sequence-specific double-stranded DNA binding activity. Involved in negative regulation of transcription, DNA-templated; positive regulation of transcription, DNA-templated; and regulation of transcription by RNA polymerase II. Located in cytosol and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PP5: Variant 4-139137692-C-T is Pathogenic according to our data. Variant chr4-139137692-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 431175.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.28851974). . Strength limited to SUPPORTING due to the PP5.
• BS2: High AC in GnomAdExome4 at 33 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ELF2	NM_001331036.3	c.10G>A	p.Ala4Thr	missense_variant	Exon 3 of 10	ENST00000686138.1	NP_001317965.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ELF2	ENST00000686138.1	c.10G>A	p.Ala4Thr	missense_variant	Exon 3 of 10		NM_001331036.3	ENSP00000510098.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000226 AC: 33 AN: 1461666 Hom.: 0 Cov.: 30 AF XY: 0.0000220 AC XY: 16 AN XY: 727136

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: 0.0000297

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1 Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome Pathogenic:1

Aug 03, 2017

Otology & Neurotology- Genomics of vestibular disorders (CTS-495), Jose Antonio López Escámez, Centro Pfizer - Universidad de Granada - Junta de Andalucía de Genómica e Investigación Oncológica (GENYO)

Significance: Likely pathogenic

Review Status: criteria provided, single submitter

Collection Method: in vitro;research

Regulates the expression of ATXN2 and ELOVL5 genes, two Ataxia genes. -

not provided Uncertain:1

May 03, 2022

OMIM

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.029	.;T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.92	D;D
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.7	L;L
PROVEAN	Benign	-0.44	N;N
REVEL	Benign	0.12
Sift	Benign	0.066	T;T
Sift4G	Benign	0.16	T;T
Polyphen		1.0	D;.
Vest4		0.33
MutPred		0.20		Gain of relative solvent accessibility (P = 0.09);Gain of relative solvent accessibility (P = 0.09);
MVP		0.38
MPC		0.33
ClinPred		0.74	D
GERP RS		5.2
Varity_R		0.12
gMVP		0.32

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

Other links and lift over

dbSNP: rs747574524; hg19: chr4-140058846;