8-94646298-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.48

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
ESRP1	NM_017697.4	c.490+16T>C		intron_variant		ENST00000433389.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESRP1	ENST00000433389.8	c.490+16T>C		intron_variant		1	NM_017697.4	P3

Frequencies

GnomAD3 genomes AF: 0.589 AC: 89487 AN: 151884 Hom.: 29558 Cov.: 33

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

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.: 17 AF XY: 0.704 AC XY: 454437 AN XY: 645798

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.: 33 AF XY: 0.597 AC XY: 44385 AN XY: 74298

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hearing loss, autosomal recessive 109 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	11
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

Other links and lift over

dbSNP: rs60139063; hg19: chr8-95658526; COSMIC: COSV64407892;