8-28184670-A-G

Variant names:

• chr8-28184670-A-G
• rs4732838
• NM_018091.6:c.1568-4979A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018091.6(ELP3):​c.1568-4979A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 151,972 control chromosomes in the GnomAD database, including 20,806 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.52 (20806 hom., cov: 32)
• Consequence: ELP3 NM_018091.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187
• Publications: 11 publications found

Genes affected

ELP3 (HGNC:20696): (elongator acetyltransferase complex subunit 3) Enables acetyltransferase activity and phosphorylase kinase regulator activity. Involved in regulation of transcription by RNA polymerase II and tRNA wobble uridine modification. Located in cytosol and nucleolus. Part of elongator holoenzyme complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000309630 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018091.6. 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
	ELP3	NM_018091.6	MANE Select	c.1568-4979A>G		intron	N/A	NP_060561.3
	ELP3	NM_001284222.2		c.1526-4979A>G		intron	N/A	NP_001271151.1	Q9H9T3-2
	ELP3	NM_001284220.2		c.1352-4979A>G		intron	N/A	NP_001271149.1	B4DKA4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ELP3	ENST00000256398.13	TSL:1 MANE Select	c.1568-4979A>G		intron	N/A	ENSP00000256398.8	Q9H9T3-1
	ELP3	ENST00000521015.5	TSL:1	c.1526-4979A>G		intron	N/A	ENSP00000428449.1	Q9H9T3-2
	ELP3	ENST00000900018.1		c.1688-4979A>G		intron	N/A	ENSP00000570077.1

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79071 AN: 151854 Hom.: 20800 Cov.: 32

Gnomad AFR AF: 0.447

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.554

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

GnomAD4 genome AF: 0.521 AC: 79106 AN: 151972 Hom.: 20806 Cov.: 32 AF XY: 0.515 AC XY: 38245 AN XY: 74238

African (AFR) AF: 0.447 AC: 18523 AN: 41468

American (AMR) AF: 0.534 AC: 8152 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 2153 AN: 3472

East Asian (EAS) AF: 0.420 AC: 2171 AN: 5172

South Asian (SAS) AF: 0.445 AC: 2146 AN: 4820

European-Finnish (FIN) AF: 0.517 AC: 5453 AN: 10540

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.568 AC: 38578 AN: 67926

Other (OTH) AF: 0.548 AC: 1156 AN: 2110

Alfa AF: 0.545 Hom.: 12494

Bravo AF: 0.522

Asia WGS AF: 0.435 AC: 1514 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.4
DANN	Benign	0.75
PhyloP100		-0.19
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: rs4732838; hg19: chr8-28042187;