Variant chr1-6424907-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_031475.3(ESPN):c.-49G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 1,411,672 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 7 hom. )

Consequence

ESPN
NM_031475.3 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.196

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 1-6424907-G-A is Benign according to our data. Variant chr1-6424907-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1202200.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00178 (270/151748) while in subpopulation NFE AF= 0.00153 (104/67828). AF 95% confidence interval is 0.00129. There are 1 homozygotes in gnomad4. There are 174 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 7 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESPN	NM_031475.3 linkuse as main transcript	c.-49G>A		5_prime_UTR_variant	1/13	ENST00000645284.1	NP_113663.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESPN	ENST00000645284.1 linkuse as main transcript	c.-49G>A		5_prime_UTR_variant	1/13		NM_031475.3	ENSP00000496593	P1	B1AK53-1
ESPN	ENST00000636330.1 linkuse as main transcript	c.-49G>A		5_prime_UTR_variant	1/11	5		ENSP00000490186

Frequencies

GnomAD3 genomes

AF:

0.00178

AC:

270

AN:

151640

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00404

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0118

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00153

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00224

AC:

132

AN:

58876

Hom.:

AF XY:

0.00188

AC XY:

AN XY:

34590

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000970

Gnomad ASJ exome

AF:

0.00485

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0138

Gnomad NFE exome

AF:

0.00197

Gnomad OTH exome

AF:

0.00353

GnomAD4 exome

AF:

0.00132

AC:

1658

AN:

1259924

Hom.:

Cov.:

AF XY:

0.00122

AC XY:

754

AN XY:

618930

show subpopulations

Gnomad4 AFR exome

AF:

0.0000800

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00413

Gnomad4 EAS exome

AF:

0.0000382

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0115

Gnomad4 NFE exome

AF:

0.00112

Gnomad4 OTH exome

AF:

0.00136

GnomAD4 genome

AF:

0.00178

AC:

270

AN:

151748

Hom.:

Cov.:

AF XY:

0.00235

AC XY:

174

AN XY:

74190

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00404

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0118

Gnomad4 NFE

AF:

0.00153

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00127

Hom.:

Bravo

AF:

0.000869

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 05, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

8.0

DANN

Benign

0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

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