chr3-186048922-G-A

Position:

• chr3-186048922-G-A

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.1312-62C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 1,378,782 control chromosomes in the GnomAD database, including 29,258 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (3047 hom., cov: 32)
  • Exomes 𝑓: 0.18 (26211 hom.)
• Consequence: ETV5 NM_004454.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.666

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 3-186048922-G-A is Benign according to our data. Variant chr3-186048922-G-A is described in ClinVar as [Benign]. Clinvar id is 1263860.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.61 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ETV5	NM_004454.3	c.1312-62C>T		intron_variant		ENST00000306376.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ETV5	ENST00000306376.10	c.1312-62C>T		intron_variant		1	NM_004454.3	P1
ETV5	ENST00000434744.5	c.1312-62C>T		intron_variant		1		P1
ETV5	ENST00000433149.1	c.*53-62C>T		intron_variant, NMD_transcript_variant		5
ETV5	ENST00000480706.1	n.486-62C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24396 AN: 151980 Hom.: 3046 Cov.: 32

Gnomad AFR AF: 0.0518

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.185

GnomAD4 exome AF: 0.176 AC: 215503 AN: 1226684 Hom.: 26211 AF XY: 0.181 AC XY: 111007 AN XY: 614734

Gnomad4 AFR exome AF: 0.0510

Gnomad4 AMR exome AF: 0.362

Gnomad4 ASJ exome AF: 0.232

Gnomad4 EAS exome AF: 0.621

Gnomad4 SAS exome AF: 0.326

Gnomad4 FIN exome AF: 0.246

Gnomad4 NFE exome AF: 0.134

Gnomad4 OTH exome AF: 0.199

GnomAD4 genome AF: 0.160 AC: 24397 AN: 152098 Hom.: 3047 Cov.: 32 AF XY: 0.173 AC XY: 12896 AN XY: 74344

Gnomad4 AFR AF: 0.0517

Gnomad4 AMR AF: 0.262

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.628

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.188

Alfa AF: 0.134 Hom.: 321

Bravo AF: 0.160

Asia WGS AF: 0.449 AC: 1556 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 10, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.17
DANN	Benign	0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs79060173; hg19: chr3-185766711; COSMIC: COSV60506016;