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:):

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	Protein	UniProt
ETV5	NM_004454.3	c.-74-273A>G		intron_variant		ENST00000306376.10	NP_004445.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ETV5	ENST00000306376.10	c.-74-273A>G		intron_variant		1	NM_004454.3	ENSP00000306894.5

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

- -

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;