19-42248868-G-C

Variant names:

• chr19-42248868-G-C
• rs139842507
• NM_006494.4:c.1244C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006494.4(ERF):​c.1244C>G​(p.Ala415Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,455,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A415V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: ERF NM_006494.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0350

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]

ENSG00000268643 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06690663).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERF	NM_006494.4	c.1244C>G	p.Ala415Gly	missense_variant	Exon 4 of 4	ENST00000222329.9	NP_006485.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERF	ENST00000222329.9	c.1244C>G	p.Ala415Gly	missense_variant	Exon 4 of 4	1	NM_006494.4	ENSP00000222329.3
ENSG00000268643	ENST00000594664.1	c.22+6110C>G		intron_variant	Intron 1 of 4	3		ENSP00000470087.1
ERF	ENST00000440177.6	c.1019C>G	p.Ala340Gly	missense_variant	Exon 4 of 4	2		ENSP00000388173.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1455034 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 723628

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: 0.0000204

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	1.3
DANN	Benign	0.95
DEOGEN2	Benign	0.11	T;.
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.53	T;T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.067	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.14	N;N
REVEL	Benign	0.066
Sift	Uncertain	0.0070	D;D
Sift4G	Benign	0.54	T;T
Polyphen		0.16	B;.
Vest4		0.044
MutPred		0.11		Loss of helix (P = 0.079);.;
MVP		0.10
MPC		0.64
ClinPred		0.13	T
GERP RS		2.9
Varity_R		0.063
gMVP		0.10

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: rs139842507; hg19: chr19-42753020;