chr3-121844508-T-C

Variant names:

• chr3-121844508-T-C
• rs9884018
• NM_018456.6:c.162T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_018456.6(EAF2):​c.162T>C​(p.Gly54Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 1,608,478 control chromosomes in the GnomAD database, including 26,203 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 0.16 (2630 hom., cov: 32)
  • Exomes 𝑓: 0.16 (23573 hom.)
• Consequence: EAF2 NM_018456.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09
• Publications: 26 publications found

Genes affected

EAF2 (HGNC:23115): (ELL associated factor 2) Enables transcription elongation regulator activity. Involved in positive regulation of transcription by RNA polymerase II and regulation of transcription elongation from RNA polymerase II promoter. Part of transcription elongation factor complex. Biomarker of prostate cancer. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP7: Synonymous conserved (PhyloP=1.09 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018456.6. 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
	EAF2	NM_018456.6	MANE Select	c.162T>C	p.Gly54Gly	synonymous	Exon 2 of 6	NP_060926.2
	EAF2	NM_001320041.2		c.-92T>C		5_prime_UTR	Exon 2 of 5	NP_001306970.1	Q96CJ1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EAF2	ENST00000273668.7	TSL:1 MANE Select	c.162T>C	p.Gly54Gly	synonymous	Exon 2 of 6	ENSP00000273668.2	Q96CJ1-1
	EAF2	ENST00000490434.5	TSL:1	n.162T>C		non_coding_transcript_exon	Exon 2 of 5	ENSP00000418374.1	F8WCI9
	EAF2	ENST00000451944.2	TSL:2	c.162T>C	p.Gly54Gly	synonymous	Exon 2 of 6	ENSP00000410708.2	B4DWJ3

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24613 AN: 151958 Hom.: 2631 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.0813

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.168

Gnomad EAS AF: 0.624

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.141

Gnomad OTH AF: 0.143

GnomAD2 exomes AF: 0.178 AC: 44261 AN: 248598 AF XY: 0.179

Gnomad AFR exome AF: 0.157

Gnomad AMR exome AF: 0.128

Gnomad ASJ exome AF: 0.160

Gnomad EAS exome AF: 0.641

Gnomad FIN exome AF: 0.105

Gnomad NFE exome AF: 0.139

Gnomad OTH exome AF: 0.159

GnomAD4 exome AF: 0.158 AC: 230363 AN: 1456402 Hom.: 23573 Cov.: 30 AF XY: 0.160 AC XY: 115611 AN XY: 724568

African (AFR) AF: 0.157 AC: 5216 AN: 33274

American (AMR) AF: 0.129 AC: 5693 AN: 44130

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 4211 AN: 26016

East Asian (EAS) AF: 0.646 AC: 25296 AN: 39136

South Asian (SAS) AF: 0.181 AC: 15521 AN: 85612

European-Finnish (FIN) AF: 0.107 AC: 5726 AN: 53342

Middle Eastern (MID) AF: 0.155 AC: 889 AN: 5744

European-Non Finnish (NFE) AF: 0.142 AC: 157605 AN: 1109008

Other (OTH) AF: 0.170 AC: 10206 AN: 60140

GnomAD4 genome AF: 0.162 AC: 24642 AN: 152076 Hom.: 2630 Cov.: 32 AF XY: 0.164 AC XY: 12161 AN XY: 74338

African (AFR) AF: 0.156 AC: 6456 AN: 41492

American (AMR) AF: 0.151 AC: 2311 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.168 AC: 583 AN: 3466

East Asian (EAS) AF: 0.624 AC: 3222 AN: 5162

South Asian (SAS) AF: 0.197 AC: 949 AN: 4820

European-Finnish (FIN) AF: 0.103 AC: 1086 AN: 10578

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.141 AC: 9608 AN: 67970

Other (OTH) AF: 0.147 AC: 310 AN: 2112

Alfa AF: 0.150 Hom.: 6412

Bravo AF: 0.168

Asia WGS AF: 0.329 AC: 1138 AN: 3472

EpiCase AF: 0.147

EpiControl AF: 0.146

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	13
DANN	Benign	0.68
PhyloP100		1.1
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: rs9884018; hg19: chr3-121563355; COSMIC: COSV56543968;