NM_004454.3:c.1210-176C>A

Variant names:

• chr3-186052307-G-T
• rs74607992
• NM_004454.3:c.1210-176C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 5234 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004454.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETV5	NM_004454.3	MANE Select	c.1210-176C>A		intron	N/A	NP_004445.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETV5	ENST00000306376.10	TSL:1 MANE Select	c.1210-176C>A		intron	N/A	ENSP00000306894.5
	ETV5	ENST00000434744.5	TSL:1	c.1210-176C>A		intron	N/A	ENSP00000413755.1
	ETV5	ENST00000875747.1		c.1210-176C>A		intron	N/A	ENSP00000545806.1

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

African (AFR) AF: 0.00962 AC: 400 AN: 41566

American (AMR) AF: 0.0349 AC: 534 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0173 AC: 60 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.0106 AC: 51 AN: 4828

European-Finnish (FIN) AF: 0.0708 AC: 750 AN: 10598

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0490 AC: 3334 AN: 68020

Other (OTH) AF: 0.0354 AC: 75 AN: 2116

Alfa AF: 0.0428 Hom.: 28

Bravo AF: 0.0301

Asia WGS AF: 0.00664 AC: 26 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	16
DANN	Benign	0.49
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs74607992; hg19: chr3-185770096;