3-186048773-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_004454.3(ETV5):c.1399C>T(p.Leu467=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00146 in 1,614,142 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0080 (14 hom., cov: 32)
  • Exomes 𝑓: 0.00079 (18 hom.)
• Consequence: ETV5 NM_004454.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.88

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 3-186048773-G-A is Benign according to our data. Variant chr3-186048773-G-A is described in ClinVar as [Benign]. Clinvar id is 785073.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00797 (1214/152272) while in subpopulation AFR AF= 0.028 (1163/41544). AF 95% confidence interval is 0.0267. There are 14 homozygotes in gnomad4. There are 566 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 1213 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ETV5	NM_004454.3	c.1399C>T	p.Leu467=	synonymous_variant	13/13	ENST00000306376.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ETV5	ENST00000306376.10	c.1399C>T	p.Leu467=	synonymous_variant	13/13	1	NM_004454.3	P1
ETV5	ENST00000434744.5	c.1399C>T	p.Leu467=	synonymous_variant	13/13	1		P1
ETV5	ENST00000480706.1	n.573C>T		non_coding_transcript_exon_variant	5/5	3
ETV5	ENST00000433149.1			downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.00797 AC: 1213 AN: 152154 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.0281

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00718

GnomAD3 exomes AF: 0.00200 AC: 502 AN: 250638 Hom.: 5 AF XY: 0.00132 AC XY: 179 AN XY: 135486

Gnomad AFR exome AF: 0.0282

Gnomad AMR exome AF: 0.00104

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000266

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.000785 AC: 1148 AN: 1461870 Hom.: 18 Cov.: 31 AF XY: 0.000648 AC XY: 471 AN XY: 727238

Gnomad4 AFR exome AF: 0.0292

Gnomad4 AMR exome AF: 0.00103

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000117

Gnomad4 OTH exome AF: 0.00159

GnomAD4 genome AF: 0.00797 AC: 1214 AN: 152272 Hom.: 14 Cov.: 32 AF XY: 0.00760 AC XY: 566 AN XY: 74450

Gnomad4 AFR AF: 0.0280

Gnomad4 AMR AF: 0.00196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.00477 Hom.: 8

Bravo AF: 0.00887

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

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

Invitae

Apr 19, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	10
Dann	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs115703632; hg19: chr3-185766562;