Variant 19-42248996-GGAA-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_006494.4(ERF):c.1113_1115delTTC(p.Ser372del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000255 in 1,609,182 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00034 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00025 ( 1 hom. )

Consequence

ERF
NM_006494.4 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.29

Variant links:

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]

ERF links:

ENSG00000268643 (HGNC:):

ENSG00000268643 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 19-42248996-GGAA-G is Benign according to our data. Variant chr19-42248996-GGAA-G is described in ClinVar as [Likely_benign]. Clinvar id is 476624.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000341 (52/152314) while in subpopulation EAS AF= 0.0027 (14/5188). AF 95% confidence interval is 0.00163. There are 1 homozygotes in gnomad4. There are 21 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 52 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERF	NM_006494.4 linkuse as main transcript	c.1113_1115delTTC	p.Ser372del	disruptive_inframe_deletion	4/4	ENST00000222329.9	NP_006485.2	P50548-1A0A024R0L4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ERF	ENST00000222329.9 linkuse as main transcript	c.1113_1115delTTC	p.Ser372del	disruptive_inframe_deletion	4/4	1	NM_006494.4	ENSP00000222329.3	P50548-1
ENSG00000268643	ENST00000594664.1 linkuse as main transcript	c.22+5979_22+5981delTTC		intron_variant		3		ENSP00000470087.1	M0QYV0
ERF	ENST00000440177.6 linkuse as main transcript	c.888_890delTTC	p.Ser297del	disruptive_inframe_deletion	4/4	2		ENSP00000388173.2	P50548-2

Frequencies

GnomAD3 genomes

AF:

0.000342

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00269

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000466

AC:

111

AN:

238320

Hom.:

AF XY:

0.000437

AC XY:

AN XY:

130352

show subpopulations

Gnomad AFR exome

AF:

0.000415

Gnomad AMR exome

AF:

0.000234

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00343

Gnomad SAS exome

AF:

0.000132

Gnomad FIN exome

AF:

0.000268

Gnomad NFE exome

AF:

0.000215

Gnomad OTH exome

AF:

0.000682

GnomAD4 exome

AF:

0.000246

AC:

358

AN:

1456868

Hom.:

AF XY:

0.000258

AC XY:

187

AN XY:

724620

show subpopulations

Gnomad4 AFR exome

AF:

0.000389

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00209

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.000202

Gnomad4 NFE exome

AF:

0.000154

Gnomad4 OTH exome

AF:

0.000812

GnomAD4 genome

AF:

0.000341

AC:

AN:

152314

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.0000653

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00270

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.000473

Bravo

AF:

0.000359

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

TWIST1-related craniosynostosis

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 23, 2022

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 03, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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