3-186106215-T-C

Position:

• chr3-186106215-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ETV5	NM_004454.3	c.-74-273A>G		intron_variant		ENST00000306376.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ETV5	ENST00000306376.10	c.-74-273A>G		intron_variant		1	NM_004454.3	P1

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

Gnomad4 AFR AF: 0.820

Gnomad4 AMR AF: 0.908

Gnomad4 ASJ AF: 0.870

Gnomad4 EAS AF: 0.946

Gnomad4 SAS AF: 0.848

Gnomad4 FIN AF: 0.909

Gnomad4 NFE AF: 0.867

Gnomad4 OTH AF: 0.877

Alfa AF: 0.870 Hom.: 17724

Bravo AF: 0.862

Asia WGS AF: 0.894 AC: 3103 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.4
DANN	Benign	0.86

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: rs1516725; hg19: chr3-185824004;