Variant 8-109553948-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004215.5(EBAG9):c.162+5G>T variant causes a splice donor 5th base, 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_donor_5th_base, intron

Scores

Splicing: ADA: 0.1985

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.142

Variant links:

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]

EBAG9 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 46 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EBAG9	NM_004215.5 linkuse as main transcript	c.162+5G>T		splice_donor_5th_base_variant, intron_variant		ENST00000337573.10	NP_004206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EBAG9	ENST00000337573.10 linkuse as main transcript	c.162+5G>T		splice_donor_5th_base_variant, intron_variant		1	NM_004215.5	ENSP00000337675	P1	O00559-1

Frequencies

GnomAD3 genomes

AF:

0.0130

AC:

1974

AN:

151874

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.00357

AC:

801

AN:

224440

Hom.:

AF XY:

0.00250

AC XY:

305

AN XY:

121764

show subpopulations

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 SAS exome

AF:

0.0000398

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.:

Cov.:

AF XY:

0.00104

AC XY:

743

AN XY:

713106

show subpopulations

Gnomad4 AFR exome

AF:

0.0465

Gnomad4 AMR exome

AF:

0.00305

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000375

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000154

Gnomad4 OTH exome

AF:

0.00273

GnomAD4 genome

AF:

0.0130

AC:

1971

AN:

151992

Hom.:

Cov.:

AF XY:

0.0119

AC XY:

887

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.0446

Gnomad4 AMR

AF:

0.00623

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000736

Gnomad4 OTH

AF:

0.00951

Alfa

AF:

0.000558

Hom.:

Bravo

AF:

0.0147

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 30, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.7

DANN

Benign

0.62

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over