3-186106215-T-C

Variant names:

• chr3-186106215-T-C
• rs1516725
• NM_004454.3:c.-74-273A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004454.3(ETV5):​c.-74-273A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.863 in 152,082 control chromosomes in the GnomAD database, including 56,795 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.86 (56795 hom., cov: 30)
• Consequence: ETV5 NM_004454.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.193
• Publications: 102 publications found

Genes affected

ETV5 (HGNC:3494): (ETS variant transcription factor 5) Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in cellular response to oxidative stress; negative regulation of transcription by RNA polymerase II; and positive regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

DGKG (HGNC:2853): (diacylglycerol kinase gamma) This gene encodes an enzyme that is a member of the type I subfamily of diacylglycerol kinases, which are involved in lipid metabolism. These enzymes generate phosphatidic acid by catalyzing the phosphorylation of diacylglycerol, a fundamental lipid second messenger that activates numerous proteins, including protein kinase C isoforms, Ras guanyl nucleotide-releasing proteins and some transient receptor potential channels. Diacylglycerol kinase gamma has been implicated in cell cycle regulation and in the negative regulation of macrophage differentiation in leukemia cells. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 3-186106215-T-C is Benign according to our data. Variant chr3-186106215-T-C is described in ClinVar as Benign. ClinVar VariationId is 1227671.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004454.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETV5	NM_004454.3	MANE Select	c.-74-273A>G		intron	N/A	NP_004445.1	P41161-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETV5	ENST00000306376.10	TSL:1 MANE Select	c.-74-273A>G		intron	N/A	ENSP00000306894.5	P41161-1
	ETV5	ENST00000434744.5	TSL:1	c.-74-273A>G		intron	N/A	ENSP00000413755.1	P41161-1
	ETV5	ENST00000875747.1		c.-71-276A>G		intron	N/A	ENSP00000545806.1

Frequencies

GnomAD3 genomes AF: 0.863 AC: 131213 AN: 151964 Hom.: 56765 Cov.: 30

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.886

Gnomad AMR AF: 0.908

Gnomad ASJ AF: 0.870

Gnomad EAS AF: 0.946

Gnomad SAS AF: 0.849

Gnomad FIN AF: 0.909

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.867

Gnomad OTH AF: 0.875

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

GnomAD4 genome AF: 0.863 AC: 131294 AN: 152082 Hom.: 56795 Cov.: 30 AF XY: 0.867 AC XY: 64459 AN XY: 74354

African (AFR) AF: 0.820 AC: 33955 AN: 41430

American (AMR) AF: 0.908 AC: 13868 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.870 AC: 3019 AN: 3472

East Asian (EAS) AF: 0.946 AC: 4899 AN: 5178

South Asian (SAS) AF: 0.848 AC: 4089 AN: 4820

European-Finnish (FIN) AF: 0.909 AC: 9619 AN: 10582

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.867 AC: 58941 AN: 68014

Other (OTH) AF: 0.877 AC: 1846 AN: 2106

Alfa AF: 0.867 Hom.: 106406

Bravo AF: 0.862

Asia WGS AF: 0.894 AC: 3103 AN: 3470

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.4
DANN	Benign	0.86
PhyloP100		-0.19
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: rs1516725; hg19: chr3-185824004;