Variant 8-94664728-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017697.4(ESRP1):c.676G>A(p.Val226Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000521 in 1,613,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

ESRP1
NM_017697.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.37

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.059493512).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ESRP1	NM_017697.4 linkuse as main transcript	c.676G>A	p.Val226Ile	missense_variant	7/16	ENST00000433389.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESRP1	ENST00000433389.8 linkuse as main transcript	c.676G>A	p.Val226Ile	missense_variant	7/16	1	NM_017697.4	P3	Q6NXG1-1

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000661

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000883

AC:

AN:

249222

Hom.:

AF XY:

0.0000740

AC XY:

AN XY:

135196

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.000464

Gnomad NFE exome

AF:

0.0000354

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000472

AC:

AN:

1461642

Hom.:

Cov.:

AF XY:

0.0000495

AC XY:

AN XY:

727106

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000696

Gnomad4 FIN exome

AF:

0.000412

Gnomad4 NFE exome

AF:

0.0000270

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.0000986

AC:

AN:

152094

Hom.:

Cov.:

AF XY:

0.000162

AC XY:

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000661

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000325

Hom.:

Bravo

AF:

0.0000529

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000121

AC:

ExAC

AF:

0.0000414

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 26, 2022

The c.676G>A (p.V226I) alteration is located in exon 7 (coding exon 7) of the ESRP1 gene. This alteration results from a G to A substitution at nucleotide position 676, causing the valine (V) at amino acid position 226 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.54

Cadd

Benign

Dann

Benign

0.96

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.048

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.87

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

M_CAP

Benign

0.0041

MetaRNN

Benign

0.059

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.95

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

MutationTaster

Benign

0.98

D;D;D;D

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.53

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

REVEL

Benign

0.085

Sift

Benign

0.35

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

Sift4G

Benign

0.52

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

Polyphen

0.018, 0.030, 0.22

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

Vest4

0.16

MVP

0.25

MPC

0.44

ClinPred

0.035

GERP RS

3.6

Varity_R

0.026

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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