3-186106184-T-C

Position:

• chr3-186106184-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_004454.3(ETV5):​c.-74-242A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0237 in 152,176 control chromosomes in the GnomAD database, including 109 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.024 (109 hom., cov: 32)
• Consequence: ETV5 NM_004454.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.42

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 3-186106184-T-C is Benign according to our data. Variant chr3-186106184-T-C is described in ClinVar as [Benign]. Clinvar id is 1283692.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0749 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ETV5	NM_004454.3	c.-74-242A>G		intron_variant		ENST00000306376.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ETV5	ENST00000306376.10	c.-74-242A>G		intron_variant		1	NM_004454.3	P1

Frequencies

GnomAD3 genomes AF: 0.0236 AC: 3592 AN: 152056 Hom.: 108 Cov.: 32

Gnomad AFR AF: 0.00360

Gnomad AMI AF: 0.0595

Gnomad AMR AF: 0.0781

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.0289

Gnomad SAS AF: 0.00477

Gnomad FIN AF: 0.0937

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0143

Gnomad OTH AF: 0.0215

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

GnomAD4 genome AF: 0.0237 AC: 3605 AN: 152176 Hom.: 109 Cov.: 32 AF XY: 0.0284 AC XY: 2114 AN XY: 74404

Gnomad4 AFR AF: 0.00359

Gnomad4 AMR AF: 0.0786

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.0290

Gnomad4 SAS AF: 0.00477

Gnomad4 FIN AF: 0.0937

Gnomad4 NFE AF: 0.0143

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.0186 Hom.: 5

Bravo AF: 0.0203

Asia WGS AF: 0.0310 AC: 106 AN: 3476

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 21, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	6.1
DANN	Benign	0.92

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: rs4686731; hg19: chr3-185823973;