3-186052307-G-T

Position:

• chr3-186052307-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004454.3(ETV5):​c.1210-176C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0344 in 152,284 control chromosomes in the GnomAD database, including 113 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.034 (113 hom., cov: 32)
• Consequence: ETV5 NM_004454.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.27

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 3-186052307-G-T is Benign according to our data. Variant chr3-186052307-G-T is described in ClinVar as [Benign]. Clinvar id is 1282711.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0344 (5234/152284) while in subpopulation NFE AF= 0.049 (3334/68020). AF 95% confidence interval is 0.0476. There are 113 homozygotes in gnomad4. There are 2586 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 5234 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETV5	NM_004454.3	c.1210-176C>A		intron_variant		ENST00000306376.10	NP_004445.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ETV5	ENST00000306376.10	c.1210-176C>A		intron_variant		1	NM_004454.3	ENSP00000306894	P1
ETV5	ENST00000434744.5	c.1210-176C>A		intron_variant		1		ENSP00000413755	P1
ETV5	ENST00000433149.1	c.219-176C>A		intron_variant, NMD_transcript_variant		5		ENSP00000399707
ETV5	ENST00000480706.1	n.384-176C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0344 AC: 5235 AN: 152166 Hom.: 113 Cov.: 32

Gnomad AFR AF: 0.00965

Gnomad AMI AF: 0.0297

Gnomad AMR AF: 0.0350

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0103

Gnomad FIN AF: 0.0708

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0490

Gnomad OTH AF: 0.0358

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0344 AC: 5234 AN: 152284 Hom.: 113 Cov.: 32 AF XY: 0.0347 AC XY: 2586 AN XY: 74460

Gnomad4 AFR AF: 0.00962

Gnomad4 AMR AF: 0.0349

Gnomad4 ASJ AF: 0.0173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0106

Gnomad4 FIN AF: 0.0708

Gnomad4 NFE AF: 0.0490

Gnomad4 OTH AF: 0.0354

Alfa AF: 0.0428 Hom.: 28

Bravo AF: 0.0301

Asia WGS AF: 0.00664 AC: 26 AN: 3478

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 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Benign	0.49

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: rs74607992; hg19: chr3-185770096;