chr3-186080939-A-G

Position:

• chr3-186080939-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004454.3(ETV5):​c.362+107T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0338 in 1,352,070 control chromosomes in the GnomAD database, including 908 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.042 (176 hom., cov: 32)
  • Exomes 𝑓: 0.033 (732 hom.)
• Consequence: ETV5 NM_004454.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.890

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]

ETV5-AS1 (HGNC:40222): (ETV5 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 3-186080939-A-G is Benign according to our data. Variant chr3-186080939-A-G is described in ClinVar as [Benign]. Clinvar id is 1295077.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0696 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ETV5	NM_004454.3	c.362+107T>C		intron_variant		ENST00000306376.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ETV5	ENST00000306376.10	c.362+107T>C		intron_variant		1	NM_004454.3	P1
ETV5-AS1	ENST00000453370.1	n.552A>G		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes AF: 0.0422 AC: 6416 AN: 152170 Hom.: 174 Cov.: 32

Gnomad AFR AF: 0.0718

Gnomad AMI AF: 0.0374

Gnomad AMR AF: 0.0347

Gnomad ASJ AF: 0.0366

Gnomad EAS AF: 0.0193

Gnomad SAS AF: 0.0493

Gnomad FIN AF: 0.0253

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0301

Gnomad OTH AF: 0.0435

GnomAD4 exome AF: 0.0327 AC: 39241 AN: 1199782 Hom.: 732 Cov.: 15 AF XY: 0.0330 AC XY: 19562 AN XY: 592680

Gnomad4 AFR exome AF: 0.0758

Gnomad4 AMR exome AF: 0.0457

Gnomad4 ASJ exome AF: 0.0323

Gnomad4 EAS exome AF: 0.0198

Gnomad4 SAS exome AF: 0.0473

Gnomad4 FIN exome AF: 0.0227

Gnomad4 NFE exome AF: 0.0309

Gnomad4 OTH exome AF: 0.0330

GnomAD4 genome AF: 0.0422 AC: 6423 AN: 152288 Hom.: 176 Cov.: 32 AF XY: 0.0414 AC XY: 3080 AN XY: 74464

Gnomad4 AFR AF: 0.0717

Gnomad4 AMR AF: 0.0348

Gnomad4 ASJ AF: 0.0366

Gnomad4 EAS AF: 0.0197

Gnomad4 SAS AF: 0.0491

Gnomad4 FIN AF: 0.0253

Gnomad4 NFE AF: 0.0301

Gnomad4 OTH AF: 0.0430

Alfa AF: 0.0333 Hom.: 17

Bravo AF: 0.0456

Asia WGS AF: 0.0250 AC: 86 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.092
DANN	Benign	0.76

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: rs113586704; hg19: chr3-185798728;