chr8-109557013-A-G

Variant names:

• chr8-109557013-A-G
• rs2131124313
• NM_004215.5:c.400A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004215.5(EBAG9):​c.400A>G​(p.Thr134Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,455,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T134I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: EBAG9 NM_004215.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.61
• Publications: 0 publications found

Genes affected

EBAG9 (HGNC:3123): (estrogen receptor binding site associated antigen 9) This gene was identified as an estrogen-responsive gene. Regulation of transcription by estrogen is mediated by estrogen receptor, which binds to the estrogen-responsive element found in the 5'-flanking region of this gene. The encoded protein is a tumor-associated antigen that is expressed at high frequency in a variety of cancers. Alternate splicing results in multiple transcript variants. A pseudogene of this gene has been defined on chromosome 10. [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20673957).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004215.5. 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
	EBAG9	NM_004215.5	MANE Select	c.400A>G	p.Thr134Ala	missense	Exon 5 of 7	NP_004206.1	O00559-1
	EBAG9	NM_001278938.2		c.400A>G	p.Thr134Ala	missense	Exon 5 of 7	NP_001265867.1	O00559-1
	EBAG9	NM_198120.3		c.400A>G	p.Thr134Ala	missense	Exon 5 of 7	NP_936056.1	O00559-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EBAG9	ENST00000337573.10	TSL:1 MANE Select	c.400A>G	p.Thr134Ala	missense	Exon 5 of 7	ENSP00000337675.5	O00559-1
	EBAG9	ENST00000531677.5	TSL:1	c.400A>G	p.Thr134Ala	missense	Exon 4 of 7	ENSP00000432082.1	O00559-2
	EBAG9	ENST00000395785.7	TSL:1	c.400A>G	p.Thr134Ala	missense	Exon 5 of 7	ENSP00000379131.2	O00559-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455080 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 723964

African (AFR) AF: 0.00 AC: 0 AN: 33300

American (AMR) AF: 0.00 AC: 0 AN: 44108

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25920

East Asian (EAS) AF: 0.00 AC: 0 AN: 39332

South Asian (SAS) AF: 0.00 AC: 0 AN: 85434

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53118

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5716

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108164

Other (OTH) AF: 0.00 AC: 0 AN: 59988

GnomAD4 genome Cov.: 32

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	0.073
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		3.6
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.069
Sift	Benign	0.37	T
Sift4G	Uncertain	0.016	D
Polyphen		0.72	P
Vest4		0.20
MutPred		0.20		Loss of glycosylation at T134 (P = 0.1337)
MVP		0.20
MPC		0.32
ClinPred		0.63	D
GERP RS		5.7
Varity_R		0.12
gMVP		0.58
Mutation Taster		=43/57	disease causing

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: rs2131124313; hg19: chr8-110569242;