dbSNP rs2311045: ESPN:p.Arg303Arg (chr1-6440984-C-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_031475.3(ESPN):c.909C>G(p.Arg303Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 1,606,166 control chromosomes in the GnomAD database, including 15,663 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2335 hom., cov: 32)

Exomes 𝑓: 0.13 ( 13328 hom. )

Consequence

ESPN
NM_031475.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.998

Variant links:

Genes affected

ESPN (HGNC:13281): (espin) This gene encodes a multifunctional actin-bundling protein. It plays a major role in regulating the organization, dimensions, dynamics, and signaling capacities of the actin filament-rich, microvillus-type specializations that mediate sensory transduction in various mechanosensory and chemosensory cells. Mutations in this gene are associated with autosomal recessive neurosensory deafness, and autosomal dominant sensorineural deafness without vestibular involvement. [provided by RefSeq, Nov 2009]

ESPN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 1-6440984-C-G is Benign according to our data. Variant chr1-6440984-C-G is described in ClinVar as [Benign]. Clinvar id is 226636.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-6440984-C-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.998 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESPN	NM_031475.3 link	c.909C>G	p.Arg303Arg	synonymous_variant	Exon 5 of 13	ENST00000645284.1	NP_113663.2	B1AK53-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESPN	ENST00000645284.1 link	c.909C>G	p.Arg303Arg	synonymous_variant	Exon 5 of 13		NM_031475.3	ENSP00000496593.1		B1AK53-1

Frequencies

GnomAD3 genomes

AF:

0.165

AC:

25015

AN:

152018

Hom.:

2331

Cov.:

show subpopulations

Gnomad AFR

AF:

0.249

Gnomad AMI

AF:

0.193

Gnomad AMR

AF:

0.119

Gnomad ASJ

AF:

0.168

Gnomad EAS

AF:

0.162

Gnomad SAS

AF:

0.168

Gnomad FIN

AF:

0.127

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.129

Gnomad OTH

AF:

0.158

GnomAD3 exomes

AF:

0.136

AC:

31699

AN:

232850

Hom.:

2344

AF XY:

0.138

AC XY:

17556

AN XY:

127514

show subpopulations

Gnomad AFR exome

AF:

0.243

Gnomad AMR exome

AF:

0.0837

Gnomad ASJ exome

AF:

0.180

Gnomad EAS exome

AF:

0.157

Gnomad SAS exome

AF:

0.162

Gnomad FIN exome

AF:

0.125

Gnomad NFE exome

AF:

0.126

Gnomad OTH exome

AF:

0.135

GnomAD4 exome

AF:

0.132

AC:

191864

AN:

1454030

Hom.:

13328

Cov.:

AF XY:

0.133

AC XY:

96018

AN XY:

722742

show subpopulations

Gnomad4 AFR exome

AF:

0.260

Gnomad4 AMR exome

AF:

0.0882

Gnomad4 ASJ exome

AF:

0.180

Gnomad4 EAS exome

AF:

0.176

Gnomad4 SAS exome

AF:

0.161

Gnomad4 FIN exome

AF:

0.124

Gnomad4 NFE exome

AF:

0.125

Gnomad4 OTH exome

AF:

0.141

GnomAD4 genome

AF:

0.165

AC:

25041

AN:

152136

Hom.:

2335

Cov.:

AF XY:

0.164

AC XY:

12193

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.249

Gnomad4 AMR

AF:

0.119

Gnomad4 ASJ

AF:

0.168

Gnomad4 EAS

AF:

0.162

Gnomad4 SAS

AF:

0.168

Gnomad4 FIN

AF:

0.127

Gnomad4 NFE

AF:

0.128

Gnomad4 OTH

AF:

0.160

Alfa

AF:

0.0845

Hom.:

157

Bravo

AF:

0.169

Asia WGS

AF:

0.165

AC:

570

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Oct 20, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

p.Arg303Arg in exon 5 of EPSN: This variant is not expected to have clinical sig nificance because it has high frequency in the general population, does not alte r an amino acid residue and is not located within the splice consensus sequence. It has been identified in 19.5% (14152/72600) of all chromosomes by the Exome A ggregation Consortium (ExAC, http://exac.broadinstitute.org;dbSNP rs2311045). -

May 09, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:2

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

8.1

DANN

Benign

0.90

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

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