Variant 8-94646267-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_017697.4(ESRP1):c.475G>A(p.Ala159Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00168 in 1,605,696 control chromosomes in the GnomAD database, including 24 homozygotes. 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.0033 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0015 ( 22 hom. )

Consequence

ESRP1
NM_017697.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.27

Variant links:

Genes affected

ESRP1 (HGNC:25966): (epithelial splicing regulatory protein 1) ESPR1 is an epithelial cell-type-specific splicing regulator (Warzecha et al., 2009 [PubMed 19285943]).[supplied by OMIM, Aug 2009]

ESRP1 links:

ESRP1 (HGNC:):

ESRP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0036323667).

BP6

Variant 8-94646267-G-A is Benign according to our data. Variant chr8-94646267-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 781917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-94646267-G-A is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESRP1	NM_017697.4 linkuse as main transcript	c.475G>A	p.Ala159Thr	missense_variant	4/16	ENST00000433389.8	NP_060167.2	Q6NXG1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESRP1	ENST00000433389.8 linkuse as main transcript	c.475G>A	p.Ala159Thr	missense_variant	4/16	1	NM_017697.4	ENSP00000405738.2		Q6NXG1-1

Frequencies

GnomAD3 genomes

AF:

0.00331

AC:

504

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00753

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00138

Gnomad ASJ

AF:

0.0294

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00456

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.00282

AC:

695

AN:

246850

Hom.:

AF XY:

0.00290

AC XY:

389

AN XY:

133942

show subpopulations

Gnomad AFR exome

AF:

0.00831

Gnomad AMR exome

AF:

0.000826

Gnomad ASJ exome

AF:

0.0275

Gnomad EAS exome

AF:

0.000112

Gnomad SAS exome

AF:

0.00465

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000837

Gnomad OTH exome

AF:

0.00483

GnomAD4 exome

AF:

0.00150

AC:

2184

AN:

1453518

Hom.:

Cov.:

AF XY:

0.00164

AC XY:

1189

AN XY:

723572

show subpopulations

Gnomad4 AFR exome

AF:

0.00882

Gnomad4 AMR exome

AF:

0.00110

Gnomad4 ASJ exome

AF:

0.0267

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.00432

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000450

Gnomad4 OTH exome

AF:

0.00358

GnomAD4 genome

AF:

0.00333

AC:

507

AN:

152178

Hom.:

Cov.:

AF XY:

0.00312

AC XY:

232

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.00756

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.0294

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00478

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000544

Gnomad4 OTH

AF:

0.00238

Alfa

AF:

0.00227

Hom.:

Bravo

AF:

0.00368

ESP6500AA

AF:

0.00832

AC:

ESP6500EA

AF:

0.00244

AC:

ExAC

AF:

0.00254

AC:

307

Asia WGS

AF:

0.00347

AC:

AN:

3474

EpiCase

AF:

0.00170

EpiControl

AF:

0.00154

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 29, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.038

.;T;T;.;.;.;T

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.22

LIST_S2

Uncertain

0.87

D;.;D;D;D;D;D

M_CAP

Benign

0.0038

MetaRNN

Benign

0.0036

T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;L;L;L;L;.;.

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.2

N;N;.;N;.;N;N

REVEL

Benign

0.022

Sift

Benign

0.31

T;T;.;T;.;T;T

Sift4G

Benign

0.66

T;T;.;T;.;T;T

Polyphen

0.0020, 0.0090

.;B;B;B;B;.;.

Vest4

0.29

MVP

0.32

MPC

0.52

ClinPred

0.0017

GERP RS

3.6

Varity_R

0.058

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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