Variant chr11-128573095-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001143820.2(ETS1):c.36C>T(p.Pro12=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00384 in 1,602,914 control chromosomes in the GnomAD database, including 112 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 33 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 79 hom. )

Consequence

ETS1
NM_001143820.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.429

Variant links:

Genes affected

ETS1 (HGNC:3488): (ETS proto-oncogene 1, transcription factor) This gene encodes a member of the ETS family of transcription factors, which are defined by the presence of a conserved ETS DNA-binding domain that recognizes the core consensus DNA sequence GGAA/T in target genes. These proteins function either as transcriptional activators or repressors of numerous genes, and are involved in stem cell development, cell senescence and death, and tumorigenesis. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.[provided by RefSeq, Jul 2011]

ETS1 links:

LOC105369565 (HGNC:):

LOC105369565 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 11-128573095-G-A is Benign according to our data. Variant chr11-128573095-G-A is described in ClinVar as [Benign]. Clinvar id is 779381.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.429 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0125 (1899/152260) while in subpopulation AFR AF= 0.0368 (1529/41542). AF 95% confidence interval is 0.0353. There are 33 homozygotes in gnomad4. There are 871 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1899 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETS1	NM_001143820.2 linkuse as main transcript	c.36C>T	p.Pro12=	synonymous_variant	2/10	ENST00000392668.8	NP_001137292.1
LOC105369565	XR_948163.3 linkuse as main transcript	n.717+6639G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ETS1	ENST00000392668.8 linkuse as main transcript	c.36C>T	p.Pro12=	synonymous_variant	2/10	1	NM_001143820.2	ENSP00000376436	P14921-3
ETS1	ENST00000525404.5 linkuse as main transcript	n.105C>T		non_coding_transcript_exon_variant	2/4	2
ETS1	ENST00000527676.2 linkuse as main transcript	n.88C>T		non_coding_transcript_exon_variant	2/3	5

Frequencies

GnomAD3 genomes

AF:

0.0125

AC:

1898

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0369

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00465

Gnomad ASJ

AF:

0.0625

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000882

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00575

AC:

1318

AN:

229084

Hom.:

AF XY:

0.00477

AC XY:

590

AN XY:

123608

show subpopulations

Gnomad AFR exome

AF:

0.0353

Gnomad AMR exome

AF:

0.00263

Gnomad ASJ exome

AF:

0.0611

Gnomad EAS exome

AF:

0.000177

Gnomad SAS exome

AF:

0.000182

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00121

Gnomad OTH exome

AF:

0.00601

GnomAD4 exome

AF:

0.00293

AC:

4251

AN:

1450654

Hom.:

Cov.:

AF XY:

0.00283

AC XY:

2037

AN XY:

720054

show subpopulations

Gnomad4 AFR exome

AF:

0.0398

Gnomad4 AMR exome

AF:

0.00293

Gnomad4 ASJ exome

AF:

0.0592

Gnomad4 EAS exome

AF:

0.0000763

Gnomad4 SAS exome

AF:

0.000299

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000648

Gnomad4 OTH exome

AF:

0.00815

GnomAD4 genome

AF:

0.0125

AC:

1899

AN:

152260

Hom.:

Cov.:

AF XY:

0.0117

AC XY:

871

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0368

Gnomad4 AMR

AF:

0.00464

Gnomad4 ASJ

AF:

0.0625

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000882

Gnomad4 OTH

AF:

0.00992

Alfa

AF:

0.0112

Hom.:

Bravo

AF:

0.0138

Asia WGS

AF:

0.00491

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.9

DANN

Benign

0.58

Splicing

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