19-42249565-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006494.4(ERF):c.547C>G(p.Arg183Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,246 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: ERF NM_006494.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.55

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3534283).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERF	NM_006494.4	c.547C>G	p.Arg183Gly	missense_variant	4/4	ENST00000222329.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERF	ENST00000222329.9	c.547C>G	p.Arg183Gly	missense_variant	4/4	1	NM_006494.4	P1
ERF	ENST00000595448.1	n.520C>G		non_coding_transcript_exon_variant	2/2	1
ERF	ENST00000440177.6	c.322C>G	p.Arg108Gly	missense_variant	4/4	2
ERF	ENST00000593944.5			downstream_gene_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000403 AC: 1 AN: 248366 Hom.: 0 AF XY: 0.00000741 AC XY: 1 AN XY: 134930

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: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000894

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461246 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 726968

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Benign	-0.037	T
BayesDel_noAF	Benign	-0.29
Cadd	Pathogenic	27
Dann	Uncertain	1.0
DEOGEN2	Benign	0.33	T;.
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.15
Sift	Uncertain	0.0080	D;D
Sift4G	Uncertain	0.057	T;T
Polyphen		0.99	D;.
Vest4		0.51
MutPred		0.33		Loss of sheet (P = 0.0025);.;
MVP		0.59
MPC		1.6
ClinPred		0.78	D
GERP RS		1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.57

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: rs587777006; hg19: chr19-42753717;