rs777157009

Variant names:

• chr3-121857039-C-G
• rs777157009
• NM_018456.6:c.367C>G

Your query was ambiguous. Multiple possible variants found:

• chr3-121857039-C-G
• chr3-121857039-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001320041.2(EAF2):​c.-24C>G variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00000411 in 1,460,918 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: EAF2 NM_001320041.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.04
• Publications: 3 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32950756).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320041.2. 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.367C>G	p.Arg123Gly	missense	Exon 4 of 6	NP_060926.2
	EAF2	NM_001320041.2		c.-24C>G		5_prime_UTR_premature_start_codon_gain	Exon 3 of 5	NP_001306970.1	Q96CJ1-2
	EAF2	NM_001320041.2		c.-24C>G		5_prime_UTR	Exon 3 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.367C>G	p.Arg123Gly	missense	Exon 4 of 6	ENSP00000273668.2	Q96CJ1-1
	EAF2	ENST00000490434.5	TSL:1	n.*23C>G		non_coding_transcript_exon	Exon 3 of 5	ENSP00000418374.1	F8WCI9
	EAF2	ENST00000490434.5	TSL:1	n.*23C>G		3_prime_UTR	Exon 3 of 5	ENSP00000418374.1	F8WCI9

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000399 AC: 1 AN: 250334 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1460918 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 726786

African (AFR) AF: 0.0000299 AC: 1 AN: 33440

American (AMR) AF: 0.00 AC: 0 AN: 44516

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39622

South Asian (SAS) AF: 0.00 AC: 0 AN: 86092

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111626

Other (OTH) AF: 0.00 AC: 0 AN: 60350

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.033	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.19
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		4.0
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.36
Sift	Benign	0.034	D
Sift4G	Benign	0.24	T
Polyphen		0.70	P
Vest4		0.66
MutPred		0.23		Loss of MoRF binding (P = 0.017)
MVP		0.23
MPC		0.14
ClinPred		0.36	T
GERP RS		1.8
Varity_R		0.099
gMVP		0.51
Mutation Taster		=52/48	polymorphism

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: rs777157009; hg19: chr3-121575886;