NM_001079675.5:c.1129-107C>T

Variant names:

• chr17-43529343-G-A
• rs12948553
• NM_001079675.5:c.1129-107C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001079675.5(ETV4):​c.1129-107C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 1,397,198 control chromosomes in the GnomAD database, including 11,175 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1304 hom., cov: 31)
  • Exomes 𝑓: 0.12 (9871 hom.)
• Consequence: ETV4 NM_001079675.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.03
• Publications: 2 publications found

Genes affected

ETV4 (HGNC:3493): (ETS variant transcription factor 4) Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in positive regulation of keratinocyte differentiation and positive regulation of transcription by RNA polymerase II. Located in chromosome and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

DHX8 (HGNC:2749): (DEAH-box helicase 8) This gene is a member of the DEAH box polypeptide family. The encoded protein contains the DEAH (Asp-Glu-Ala-His) motif which is characteristic of all DEAH box proteins, and is thought to function as an ATP-dependent RNA helicase that regulates the release of spliced mRNAs from spliceosomes prior to their export from the nucleus. This protein may be required for the replication of human immunodeficiency virus type 1 (HIV-1). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 17-43529343-G-A is Benign according to our data. Variant chr17-43529343-G-A is described in ClinVar as Benign. ClinVar VariationId is 1266831.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001079675.5. 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
	ETV4	NM_001079675.5	MANE Select	c.1129-107C>T		intron	N/A	NP_001073143.1	P43268-1
	DHX8	NM_001322219.2		c.3444-7069G>A		intron	N/A	NP_001309148.1	K7END7
	ETV4	NM_001369366.2		c.1129-107C>T		intron	N/A	NP_001356295.1	P43268-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETV4	ENST00000319349.10	TSL:1 MANE Select	c.1129-107C>T		intron	N/A	ENSP00000321835.4	P43268-1
	ETV4	ENST00000393664.6	TSL:1	c.1129-107C>T		intron	N/A	ENSP00000377273.1	P43268-1
	ETV4	ENST00000591713.5	TSL:1	c.1129-107C>T		intron	N/A	ENSP00000465718.1	P43268-1

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19139 AN: 151950 Hom.: 1305 Cov.: 31

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.0830

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.0859

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.113

GnomAD4 exome AF: 0.122 AC: 151669 AN: 1245130 Hom.: 9871 Cov.: 17 AF XY: 0.120 AC XY: 75495 AN XY: 626602

African (AFR) AF: 0.143 AC: 4172 AN: 29082

American (AMR) AF: 0.0627 AC: 2587 AN: 41260

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 2812 AN: 23916

East Asian (EAS) AF: 0.0126 AC: 483 AN: 38268

South Asian (SAS) AF: 0.0845 AC: 6748 AN: 79872

European-Finnish (FIN) AF: 0.136 AC: 7098 AN: 52368

Middle Eastern (MID) AF: 0.105 AC: 543 AN: 5182

European-Non Finnish (NFE) AF: 0.131 AC: 121161 AN: 922006

Other (OTH) AF: 0.114 AC: 6065 AN: 53176

GnomAD4 genome AF: 0.126 AC: 19146 AN: 152068 Hom.: 1304 Cov.: 31 AF XY: 0.124 AC XY: 9187 AN XY: 74324

African (AFR) AF: 0.145 AC: 6021 AN: 41458

American (AMR) AF: 0.0829 AC: 1267 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 400 AN: 3470

East Asian (EAS) AF: 0.0104 AC: 54 AN: 5172

South Asian (SAS) AF: 0.0845 AC: 407 AN: 4816

European-Finnish (FIN) AF: 0.139 AC: 1474 AN: 10570

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9080 AN: 67990

Other (OTH) AF: 0.112 AC: 237 AN: 2112

Alfa AF: 0.129 Hom.: 165

Bravo AF: 0.122

Asia WGS AF: 0.0660 AC: 231 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	-0.72
CADD	Benign	9.6
DANN	Benign	0.64
PhyloP100		1.0
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: rs12948553; hg19: chr17-41606711;