8-94643368-T-C

Variant names:

• chr8-94643368-T-C
• rs72676907
• NM_017697.4:c.327T>C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_017697.4(ESRP1):​c.327T>C​(p.Asp109Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,612,560 control chromosomes in the GnomAD database, including 24,590 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.13 (1724 hom., cov: 33)
  • Exomes 𝑓: 0.17 (22866 hom.)
• Consequence: ESRP1 NM_017697.4 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.372

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=-0.6).
• BP6: Variant 8-94643368-T-C is Benign according to our data. Variant chr8-94643368-T-C is described in ClinVar as [Benign]. Clinvar id is 3060039.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.372 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESRP1	NM_017697.4	c.327T>C	p.Asp109Asp	synonymous_variant	Exon 3 of 16	ENST00000433389.8	NP_060167.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESRP1	ENST00000433389.8	c.327T>C	p.Asp109Asp	synonymous_variant	Exon 3 of 16	1	NM_017697.4	ENSP00000405738.2

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19440 AN: 152112 Hom.: 1723 Cov.: 33

Gnomad AFR AF: 0.0285

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.0848

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0929

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.128

GnomAD3 exomes AF: 0.142 AC: 35376 AN: 249150 Hom.: 3303 AF XY: 0.145 AC XY: 19618 AN XY: 135178

Gnomad AFR exome AF: 0.0276

Gnomad AMR exome AF: 0.0753

Gnomad ASJ exome AF: 0.116

Gnomad EAS exome AF: 0.000723

Gnomad SAS exome AF: 0.109

Gnomad FIN exome AF: 0.260

Gnomad NFE exome AF: 0.188

Gnomad OTH exome AF: 0.164

GnomAD4 exome AF: 0.168 AC: 245489 AN: 1460328 Hom.: 22866 Cov.: 30 AF XY: 0.167 AC XY: 121609 AN XY: 726494

Gnomad4 AFR exome AF: 0.0272

Gnomad4 AMR exome AF: 0.0778

Gnomad4 ASJ exome AF: 0.118

Gnomad4 EAS exome AF: 0.000504

Gnomad4 SAS exome AF: 0.115

Gnomad4 FIN exome AF: 0.263

Gnomad4 NFE exome AF: 0.184

Gnomad4 OTH exome AF: 0.151

GnomAD4 genome AF: 0.128 AC: 19434 AN: 152232 Hom.: 1724 Cov.: 33 AF XY: 0.130 AC XY: 9643 AN XY: 74432

Gnomad4 AFR AF: 0.0284

Gnomad4 AMR AF: 0.0847

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0928

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.189

Gnomad4 OTH AF: 0.127

Alfa AF: 0.159 Hom.: 1229

Bravo AF: 0.110

Asia WGS AF: 0.0380 AC: 133 AN: 3478

EpiCase AF: 0.187

EpiControl AF: 0.181

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ESRP1-related disorder Benign:1

Oct 30, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as 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	-0.60
CADD	Benign	5.6
DANN	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs72676907; hg19: chr8-95655596; COSMIC: COSV64407488; COSMIC: COSV64407488;