chr3-121844508-T-C

Position:

• chr3-121844508-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000273668.7(EAF2):​c.162T>C​(p.Gly54=) 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 ENST00000273668.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EAF2	NM_018456.6	c.162T>C	p.Gly54=	synonymous_variant	2/6	ENST00000273668.7	NP_060926.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EAF2	ENST00000273668.7	c.162T>C	p.Gly54=	synonymous_variant	2/6	1	NM_018456.6	ENSP00000273668	P1
EAF2	ENST00000490434.5	c.162T>C	p.Gly54=	synonymous_variant, NMD_transcript_variant	2/5	1		ENSP00000418374
EAF2	ENST00000451944.2	c.162T>C	p.Gly54=	synonymous_variant	2/6	2		ENSP00000410708
EAF2	ENST00000490477.1	c.*204T>C		3_prime_UTR_variant, NMD_transcript_variant	3/5	3		ENSP00000419552

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

GnomAD3 exomes AF: 0.178 AC: 44261 AN: 248598 Hom.: 6123 AF XY: 0.179 AC XY: 24004 AN XY: 134458

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 SAS exome AF: 0.179

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

Gnomad4 AFR exome AF: 0.157

Gnomad4 AMR exome AF: 0.129

Gnomad4 ASJ exome AF: 0.162

Gnomad4 EAS exome AF: 0.646

Gnomad4 SAS exome AF: 0.181

Gnomad4 FIN exome AF: 0.107

Gnomad4 NFE exome AF: 0.142

Gnomad4 OTH exome AF: 0.170

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

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.168

Gnomad4 EAS AF: 0.624

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.141

Gnomad4 OTH AF: 0.147

Alfa AF: 0.150 Hom.: 4506

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	13
DANN	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs9884018; hg19: chr3-121563355; COSMIC: COSV56543968;