Variant 12-131960721-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6BP7

The NM_015409.5(EP400):c.102A>C(p.Pro34=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.033 ( 0 hom., cov: 0)

Exomes 𝑓: 0.023 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EP400
NM_015409.5 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.36

Variant links:

Genes affected

EP400 (HGNC:11958): (E1A binding protein p400) Predicted to enable several functions, including ATP binding activity; ATP-dependent chromatin remodeler activity; and protein antigen binding activity. Involved in histone H2A acetylation and histone H4 acetylation. Part of NuA4 histone acetyltransferase complex and Swr1 complex. [provided by Alliance of Genome Resources, Apr 2022]

EP400 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 12-131960721-A-C is Benign according to our data. Variant chr12-131960721-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 3033301.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-1.36 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EP400	NM_015409.5 linkuse as main transcript	c.102A>C	p.Pro34=	synonymous_variant	2/53	ENST00000389561.7	NP_056224.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EP400	ENST00000389561.7 linkuse as main transcript	c.102A>C	p.Pro34=	synonymous_variant	2/53	5	NM_015409.5	ENSP00000374212	P1	Q96L91-2
EP400	ENST00000333577.8 linkuse as main transcript	c.102A>C	p.Pro34=	synonymous_variant	2/13	1		ENSP00000333602
EP400	ENST00000332482.8 linkuse as main transcript	c.102A>C	p.Pro34=	synonymous_variant	2/8	1		ENSP00000331737
EP400	ENST00000703283.1 linkuse as main transcript	c.102A>C	p.Pro34=	synonymous_variant	1/11			ENSP00000515253

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

683

AN:

20598

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0426

Gnomad AMI

AF:

0.0141

Gnomad AMR

AF:

0.0637

Gnomad ASJ

AF:

0.0152

Gnomad EAS

AF:

0.00988

Gnomad SAS

AF:

0.0129

Gnomad FIN

AF:

0.0408

Gnomad MID

AF:

0.0278

Gnomad NFE

AF:

0.0233

Gnomad OTH

AF:

0.0581

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0233

AC:

3457

AN:

148066

Hom.:

Cov.:

AF XY:

0.0260

AC XY:

2067

AN XY:

79442

show subpopulations

Gnomad4 AFR exome

AF:

0.0243

Gnomad4 AMR exome

AF:

0.0235

Gnomad4 ASJ exome

AF:

0.0261

Gnomad4 EAS exome

AF:

0.0345

Gnomad4 SAS exome

AF:

0.0313

Gnomad4 FIN exome

AF:

0.00580

Gnomad4 NFE exome

AF:

0.0239

Gnomad4 OTH exome

AF:

0.0320

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0332

AC:

685

AN:

20624

Hom.:

Cov.:

AF XY:

0.0368

AC XY:

375

AN XY:

10194

show subpopulations

Gnomad4 AFR

AF:

0.0426

Gnomad4 AMR

AF:

0.0637

Gnomad4 ASJ

AF:

0.0152

Gnomad4 EAS

AF:

0.00984

Gnomad4 SAS

AF:

0.0129

Gnomad4 FIN

AF:

0.0408

Gnomad4 NFE

AF:

0.0233

Gnomad4 OTH

AF:

0.0597

Alfa

AF:

0.0157

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

EP400-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 13, 2020

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.94

DANN

Benign

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

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