chr3-186106184-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 ENST00000306376.10(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 ENST00000306376.10 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:):

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	Protein	UniProt
ETV5	NM_004454.3	c.-74-242A>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.-74-242A>G		intron_variant		1	NM_004454.3	ENSP00000306894.5

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

- -

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;