chr3-186080236-C-T

Variant names:

• chr3-186080236-C-T
• rs77805826
• NM_004454.3:c.363-132G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 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]

ETV5-AS1 (HGNC:40222): (ETV5 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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.363-132G>A		intron	N/A	NP_004445.1	P41161-1
	ETV5-AS1	NR_046594.1		n.173-324C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETV5	ENST00000306376.10	TSL:1 MANE Select	c.363-132G>A		intron	N/A	ENSP00000306894.5	P41161-1
	ETV5	ENST00000434744.5	TSL:1	c.363-132G>A		intron	N/A	ENSP00000413755.1	P41161-1
	ETV5	ENST00000875747.1		c.363-132G>A		intron	N/A	ENSP00000545806.1

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

African (AFR) AF: 0.134 AC: 1390 AN: 10400

American (AMR) AF: 0.0786 AC: 639 AN: 8126

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 1678 AN: 12328

East Asian (EAS) AF: 0.0217 AC: 520 AN: 23978

South Asian (SAS) AF: 0.158 AC: 4016 AN: 25452

European-Finnish (FIN) AF: 0.0930 AC: 3049 AN: 32794

Middle Eastern (MID) AF: 0.151 AC: 294 AN: 1952

European-Non Finnish (NFE) AF: 0.128 AC: 44299 AN: 344780

Other (OTH) AF: 0.131 AC: 3411 AN: 26076

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

African (AFR) AF: 0.137 AC: 5700 AN: 41504

American (AMR) AF: 0.0890 AC: 1361 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 458 AN: 3472

East Asian (EAS) AF: 0.0538 AC: 279 AN: 5188

South Asian (SAS) AF: 0.160 AC: 772 AN: 4810

European-Finnish (FIN) AF: 0.0910 AC: 965 AN: 10606

Middle Eastern (MID) AF: 0.137 AC: 40 AN: 292

European-Non Finnish (NFE) AF: 0.133 AC: 9018 AN: 68020

Other (OTH) AF: 0.116 AC: 245 AN: 2114

Alfa AF: 0.125 Hom.: 165

Bravo AF: 0.125

Asia WGS AF: 0.105 AC: 367 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.2
DANN	Benign	0.81
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

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: rs77805826; hg19: chr3-185798025;