8-109553948-G-T

Variant names:

• chr8-109553948-G-T
• rs73700652
• NM_004215.5:c.162+5G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_004215.5(EBAG9):​c.162+5G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00237 in 1,586,872 control chromosomes in the GnomAD database, including 91 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (46 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (45 hom.)
• Consequence: EBAG9 NM_004215.5 splice_region, intron
• Scores: Splicing: ADA: 0.1985
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.142
• Publications: 1 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 8-109553948-G-T is Benign according to our data. Variant chr8-109553948-G-T is described in ClinVar as Benign. ClinVar VariationId is 782515.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.013 (1971/151992) while in subpopulation AFR AF = 0.0446 (1850/41456). AF 95% confidence interval is 0.0429. There are 46 homozygotes in GnomAd4. There are 887 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 46 gene

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.162+5G>T		splice_region intron	N/A	NP_004206.1	O00559-1
	EBAG9	NM_001278938.2		c.162+5G>T		splice_region intron	N/A	NP_001265867.1	O00559-1
	EBAG9	NM_198120.3		c.162+5G>T		splice_region intron	N/A	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.162+5G>T		splice_region intron	N/A	ENSP00000337675.5	O00559-1
	EBAG9	ENST00000531677.5	TSL:1	c.162+5G>T		splice_region intron	N/A	ENSP00000432082.1	O00559-2
	EBAG9	ENST00000395785.7	TSL:1	c.162+5G>T		splice_region intron	N/A	ENSP00000379131.2	O00559-1

Frequencies

GnomAD3 genomes AF: 0.0130 AC: 1974 AN: 151874 Hom.: 46 Cov.: 32

Gnomad AFR AF: 0.0448

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00623

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000736

Gnomad OTH AF: 0.00961

GnomAD2 exomes AF: 0.00357 AC: 801 AN: 224440 AF XY: 0.00250

Gnomad AFR exome AF: 0.0493

Gnomad AMR exome AF: 0.00262

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000379

Gnomad OTH exome AF: 0.00246

GnomAD4 exome AF: 0.00125 AC: 1787 AN: 1434880 Hom.: 45 Cov.: 28 AF XY: 0.00104 AC XY: 743 AN XY: 713106

African (AFR) AF: 0.0465 AC: 1478 AN: 31766

American (AMR) AF: 0.00305 AC: 123 AN: 40276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25688

East Asian (EAS) AF: 0.00 AC: 0 AN: 38470

South Asian (SAS) AF: 0.0000375 AC: 3 AN: 79950

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53128

Middle Eastern (MID) AF: 0.000701 AC: 4 AN: 5706

European-Non Finnish (NFE) AF: 0.0000154 AC: 17 AN: 1100574

Other (OTH) AF: 0.00273 AC: 162 AN: 59322

GnomAD4 genome AF: 0.0130 AC: 1971 AN: 151992 Hom.: 46 Cov.: 32 AF XY: 0.0119 AC XY: 887 AN XY: 74298

African (AFR) AF: 0.0446 AC: 1850 AN: 41456

American (AMR) AF: 0.00623 AC: 95 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3460

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10568

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000736 AC: 5 AN: 67946

Other (OTH) AF: 0.00951 AC: 20 AN: 2104

Alfa AF: 0.00117 Hom.: 2

Bravo AF: 0.0147

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.7
DANN	Benign	0.62
PhyloP100		-0.14
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.20
dbscSNV1_RF	Benign	0.21
SpliceAI score (max)		0.030		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: rs73700652; hg19: chr8-110566177;