chr3-121879450-A-G

Position:

• chr3-121879450-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018456.6(EAF2):​c.736+6662A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 151,986 control chromosomes in the GnomAD database, including 5,194 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 0.25 (5194 hom., cov: 32)
• Consequence: EAF2 NM_018456.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EAF2	NM_018456.6	c.736+6662A>G		intron_variant		ENST00000273668.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EAF2	ENST00000273668.7	c.736+6662A>G		intron_variant		1	NM_018456.6	P1
EAF2	ENST00000490434.5	c.*392+6662A>G		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38438 AN: 151868 Hom.: 5182 Cov.: 32

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.260

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

GnomAD4 genome AF: 0.253 AC: 38483 AN: 151986 Hom.: 5194 Cov.: 32 AF XY: 0.256 AC XY: 19003 AN XY: 74312

Gnomad4 AFR AF: 0.318

Gnomad4 AMR AF: 0.262

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.390

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.257

Alfa AF: 0.255 Hom.: 839

Bravo AF: 0.256

Asia WGS AF: 0.302 AC: 1046 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.72

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: rs2332056; hg19: chr3-121598297;