rs55989313

Variant names:

• chr17-43528880-T-C
• rs55989313
• NM_001079675.5:c.1231-137A>G

Your query was ambiguous. Multiple possible variants found:

• chr17-43528880-T-C
• chr17-43528880-T-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001079675.5(ETV4):​c.1231-137A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 725,604 control chromosomes in the GnomAD database, including 24,094 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4141 hom., cov: 31)
  • Exomes 𝑓: 0.26 (19953 hom.)
• Consequence: ETV4 NM_001079675.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.112
• Publications: 7 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 17-43528880-T-C is Benign according to our data. Variant chr17-43528880-T-C is described in ClinVar as Benign. ClinVar VariationId is 1243936.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.31 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.1231-137A>G		intron	N/A	NP_001073143.1	P43268-1
	DHX8	NM_001322219.2		c.3443+6654T>C		intron	N/A	NP_001309148.1	K7END7
	ETV4	NM_001369366.2		c.1231-137A>G		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.1231-137A>G		intron	N/A	ENSP00000321835.4	P43268-1
	ETV4	ENST00000393664.6	TSL:1	c.1231-137A>G		intron	N/A	ENSP00000377273.1	P43268-1
	ETV4	ENST00000591713.5	TSL:1	c.1231-137A>G		intron	N/A	ENSP00000465718.1	P43268-1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34380 AN: 151956 Hom.: 4141 Cov.: 31

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.244

GnomAD4 exome AF: 0.259 AC: 148507 AN: 573530 Hom.: 19953 AF XY: 0.260 AC XY: 77592 AN XY: 297886

African (AFR) AF: 0.149 AC: 2180 AN: 14680

American (AMR) AF: 0.215 AC: 4507 AN: 20986

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 4377 AN: 14682

East Asian (EAS) AF: 0.370 AC: 11732 AN: 31694

South Asian (SAS) AF: 0.265 AC: 13063 AN: 49278

European-Finnish (FIN) AF: 0.277 AC: 11858 AN: 42734

Middle Eastern (MID) AF: 0.300 AC: 854 AN: 2848

European-Non Finnish (NFE) AF: 0.253 AC: 92653 AN: 366714

Other (OTH) AF: 0.243 AC: 7283 AN: 29914

GnomAD4 genome AF: 0.226 AC: 34381 AN: 152074 Hom.: 4141 Cov.: 31 AF XY: 0.229 AC XY: 16996 AN XY: 74334

African (AFR) AF: 0.146 AC: 6053 AN: 41522

American (AMR) AF: 0.211 AC: 3231 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 1069 AN: 3468

East Asian (EAS) AF: 0.323 AC: 1668 AN: 5160

South Asian (SAS) AF: 0.267 AC: 1287 AN: 4816

European-Finnish (FIN) AF: 0.281 AC: 2969 AN: 10564

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.254 AC: 17290 AN: 67948

Other (OTH) AF: 0.241 AC: 508 AN: 2108

Alfa AF: 0.133 Hom.: 229

Bravo AF: 0.218

Asia WGS AF: 0.222 AC: 772 AN: 3478

ClinVar

ClinVar submissions

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	-0.91
CADD	Benign	7.8
DANN	Benign	0.75
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs55989313; hg19: chr17-41606248; COSMIC: COSV52251631; COSMIC: COSV52251631;