3-186106153-C-T

Position:

• chr3-186106153-C-T

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.-74-211G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0792 in 152,028 control chromosomes in the GnomAD database, including 1,284 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.079 (1284 hom., cov: 32)
• Consequence: ETV5 NM_004454.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0860

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=-0.67).
• BP6: Variant 3-186106153-C-T is Benign according to our data. Variant chr3-186106153-C-T is described in ClinVar as [Benign]. Clinvar id is 1233870.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ETV5	NM_004454.3	c.-74-211G>A		intron_variant		ENST00000306376.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ETV5	ENST00000306376.10	c.-74-211G>A		intron_variant		1	NM_004454.3	P1

Frequencies

GnomAD3 genomes AF: 0.0792 AC: 12028 AN: 151910 Hom.: 1278 Cov.: 32

Gnomad AFR AF: 0.0759

Gnomad AMI AF: 0.00659

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.0262

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0781

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0275

Gnomad OTH AF: 0.0785

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

GnomAD4 genome AF: 0.0792 AC: 12043 AN: 152028 Hom.: 1284 Cov.: 32 AF XY: 0.0868 AC XY: 6448 AN XY: 74294

Gnomad4 AFR AF: 0.0757

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.0262

Gnomad4 EAS AF: 0.527

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.0781

Gnomad4 NFE AF: 0.0275

Gnomad4 OTH AF: 0.0829

Alfa AF: 0.0469 Hom.: 146

Bravo AF: 0.0900

Asia WGS AF: 0.296 AC: 1027 AN: 3478

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

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	4.0
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: rs12631658; hg19: chr3-185823942;