chr12-11657200-A-G

Variant names:

• chr12-11657200-A-G
• rs10491985
• NM_001987.5:c.33+7040A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001987.5(ETV6):​c.33+7040A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0184 in 152,338 control chromosomes in the GnomAD database, including 145 homozygotes. 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: 𝑓 0.018 (145 hom., cov: 32)
• Consequence: ETV6 NM_001987.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0970
• Publications: 1 publications found

Genes affected

ETV6 (HGNC:3495): (ETS variant transcription factor 6) This gene encodes an ETS family transcription factor. The product of this gene contains two functional domains: a N-terminal pointed (PNT) domain that is involved in protein-protein interactions with itself and other proteins, and a C-terminal DNA-binding domain. Gene knockout studies in mice suggest that it is required for hematopoiesis and maintenance of the developing vascular network. This gene is known to be involved in a large number of chromosomal rearrangements associated with leukemia and congenital fibrosarcoma. [provided by RefSeq, Sep 2008]

ETV6 Gene-Disease associations (from GenCC):

• thrombocytopenia 5

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
• acute myeloid leukemia

  Inheritance: AD, Unknown Classification: STRONG, LIMITED Submitted by: Genomics England PanelApp, Ambry Genetics
• hereditary thrombocytopenia and hematologic cancer predisposition syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ETV6	NM_001987.5	c.33+7040A>G		intron_variant	Intron 1 of 7	ENST00000396373.9	NP_001978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ETV6	ENST00000396373.9	c.33+7040A>G		intron_variant	Intron 1 of 7	1	NM_001987.5	ENSP00000379658.3
ETV6	ENST00000541426.1	n.217+7040A>G		intron_variant	Intron 1 of 3	4
ETV6	ENST00000544715.1	n.150+7040A>G		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.0184 AC: 2800 AN: 152220 Hom.: 146 Cov.: 32

Gnomad AFR AF: 0.00610

Gnomad AMI AF: 0.00769

Gnomad AMR AF: 0.0106

Gnomad ASJ AF: 0.0121

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.0486

Gnomad FIN AF: 0.00762

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0124

Gnomad OTH AF: 0.0277

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0184 AC: 2797 AN: 152338 Hom.: 145 Cov.: 32 AF XY: 0.0194 AC XY: 1446 AN XY: 74496

African (AFR) AF: 0.00609 AC: 253 AN: 41576

American (AMR) AF: 0.0106 AC: 162 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0121 AC: 42 AN: 3470

East Asian (EAS) AF: 0.214 AC: 1106 AN: 5178

South Asian (SAS) AF: 0.0487 AC: 235 AN: 4828

European-Finnish (FIN) AF: 0.00762 AC: 81 AN: 10628

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0124 AC: 843 AN: 68028

Other (OTH) AF: 0.0284 AC: 60 AN: 2114

Alfa AF: 0.0175 Hom.: 296

Bravo AF: 0.0189

Asia WGS AF: 0.112 AC: 389 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.23
DANN	Benign	0.57
PhyloP100		0.097
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10491985; hg19: chr12-11810134;