3-121872683-A-T

Variant names:

• chr3-121872683-A-T
• rs1475808486
• NM_018456.6:c.631A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_018456.6(EAF2):​c.631A>T​(p.Asn211Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: EAF2 NM_018456.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.01
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11020404).

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.631A>T	p.Asn211Tyr	missense	Exon 5 of 6	NP_060926.2
	EAF2	NM_001320041.2		c.241A>T	p.Asn81Tyr	missense	Exon 4 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.631A>T	p.Asn211Tyr	missense	Exon 5 of 6	ENSP00000273668.2	Q96CJ1-1
	EAF2	ENST00000490434.5	TSL:1	n.*287A>T		non_coding_transcript_exon	Exon 4 of 5	ENSP00000418374.1	F8WCI9
	EAF2	ENST00000490434.5	TSL:1	n.*287A>T		3_prime_UTR	Exon 4 of 5	ENSP00000418374.1	F8WCI9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1461014 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8 AN XY: 726822

African (AFR) AF: 0.000239 AC: 8 AN: 33442

American (AMR) AF: 0.00 AC: 0 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26090

East Asian (EAS) AF: 0.00 AC: 0 AN: 39608

South Asian (SAS) AF: 0.00 AC: 0 AN: 86214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111468

Other (OTH) AF: 0.0000994 AC: 6 AN: 60348

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		1.0
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.067
Sift	Benign	0.041	D
Sift4G	Uncertain	0.042	D
Polyphen		0.76	P
Vest4		0.24
MutPred		0.16		Gain of phosphorylation at N211 (P = 0.0168)
MVP		0.081
MPC		0.19
ClinPred		0.23	T
GERP RS		3.3
Varity_R		0.047
gMVP		0.15
Mutation Taster		=90/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs1475808486; hg19: chr3-121591530;