Variant 8-94646298-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_017697.4(ESRP1):c.490+16T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 1,434,470 control chromosomes in the GnomAD database, including 348,142 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 29578 hom., cov: 33)

Exomes 𝑓: 0.70 ( 318564 hom. )

Consequence

ESRP1
NM_017697.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.48

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:

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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=-0.72).

BP6

Variant 8-94646298-T-C is Benign according to our data. Variant chr8-94646298-T-C is described in ClinVar as [Benign]. Clinvar id is 1255393.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESRP1	NM_017697.4 linkuse as main transcript	c.490+16T>C		intron_variant		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.490+16T>C		intron_variant		1	NM_017697.4	ENSP00000405738.2		Q6NXG1-1

Frequencies

GnomAD3 genomes

AF:

0.589

AC:

89487

AN:

151884

Hom.:

29558

Cov.:

show subpopulations

Gnomad AFR

AF:

0.265

Gnomad AMI

AF:

0.678

Gnomad AMR

AF:

0.731

Gnomad ASJ

AF:

0.686

Gnomad EAS

AF:

0.777

Gnomad SAS

AF:

0.812

Gnomad FIN

AF:

0.703

Gnomad MID

AF:

0.758

Gnomad NFE

AF:

0.698

Gnomad OTH

AF:

0.657

GnomAD3 exomes

AF:

0.707

AC:

158520

AN:

224372

Hom.:

58060

AF XY:

0.715

AC XY:

87373

AN XY:

122116

show subpopulations

Gnomad AFR exome

AF:

0.262

Gnomad AMR exome

AF:

0.830

Gnomad ASJ exome

AF:

0.690

Gnomad EAS exome

AF:

0.780

Gnomad SAS exome

AF:

0.810

Gnomad FIN exome

AF:

0.705

Gnomad NFE exome

AF:

0.702

Gnomad OTH exome

AF:

0.729

GnomAD4 exome

AF:

0.699

AC:

897004

AN:

1282466

Hom.:

318564

Cov.:

AF XY:

0.704

AC XY:

454437

AN XY:

645798

show subpopulations

Gnomad4 AFR exome

AF:

0.258

Gnomad4 AMR exome

AF:

0.817

Gnomad4 ASJ exome

AF:

0.696

Gnomad4 EAS exome

AF:

0.766

Gnomad4 SAS exome

AF:

0.807

Gnomad4 FIN exome

AF:

0.705

Gnomad4 NFE exome

AF:

0.697

Gnomad4 OTH exome

AF:

0.691

GnomAD4 genome

AF:

0.589

AC:

89536

AN:

152004

Hom.:

29578

Cov.:

AF XY:

0.597

AC XY:

44385

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.265

Gnomad4 AMR

AF:

0.731

Gnomad4 ASJ

AF:

0.686

Gnomad4 EAS

AF:

0.778

Gnomad4 SAS

AF:

0.812

Gnomad4 FIN

AF:

0.703

Gnomad4 NFE

AF:

0.698

Gnomad4 OTH

AF:

0.660

Alfa

AF:

0.667

Hom.:

9222

Bravo

AF:

0.575

Asia WGS

AF:

0.729

AC:

2532

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hearing loss, autosomal recessive 109

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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