chr3-186080236-C-T

Position:

• chr3-186080236-C-T

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.363-132G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 638,100 control chromosomes in the GnomAD database, including 5,296 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1274 hom., cov: 32)
  • Exomes 𝑓: 0.12 (4022 hom.)
• Consequence: ETV5 NM_004454.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.183

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=-0.78).
• BP6: Variant 3-186080236-C-T is Benign according to our data. Variant chr3-186080236-C-T is described in ClinVar as [Benign]. Clinvar id is 1267175.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ETV5	NM_004454.3	c.363-132G>A		intron_variant		ENST00000306376.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ETV5	ENST00000306376.10	c.363-132G>A		intron_variant		1	NM_004454.3	P1
ETV5-AS1	ENST00000453370.1	n.173-324C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18910 AN: 152096 Hom.: 1266 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.0892

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.0540

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.0910

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.118

GnomAD4 exome AF: 0.122 AC: 59296 AN: 485886 Hom.: 4022 AF XY: 0.123 AC XY: 30206 AN XY: 245158

Gnomad4 AFR exome AF: 0.134

Gnomad4 AMR exome AF: 0.0786

Gnomad4 ASJ exome AF: 0.136

Gnomad4 EAS exome AF: 0.0217

Gnomad4 SAS exome AF: 0.158

Gnomad4 FIN exome AF: 0.0930

Gnomad4 NFE exome AF: 0.128

Gnomad4 OTH exome AF: 0.131

GnomAD4 genome AF: 0.124 AC: 18939 AN: 152214 Hom.: 1274 Cov.: 32 AF XY: 0.122 AC XY: 9043 AN XY: 74406

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.0890

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.0538

Gnomad4 SAS AF: 0.160

Gnomad4 FIN AF: 0.0910

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.116

Alfa AF: 0.125 Hom.: 165

Bravo AF: 0.125

Asia WGS AF: 0.105 AC: 367 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	Nov 11, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.2
DANN	Benign	0.81

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: rs77805826; hg19: chr3-185798025;