Variant 1-6424818-C-T 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_031475.3(ESPN):c.-138C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0483 in 883,224 control chromosomes in the GnomAD database, including 1,392 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.064 ( 398 hom., cov: 33)

Exomes 𝑓: 0.045 ( 994 hom. )

Consequence

ESPN
NM_031475.3 5_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.11

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 1-6424818-C-T is Benign according to our data. Variant chr1-6424818-C-T is described in ClinVar as [Benign]. Clinvar id is 1275204.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ESPN	NM_031475.3 linkuse as main transcript	c.-138C>T		5_prime_UTR_variant	1/13	ENST00000645284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESPN	ENST00000645284.1 linkuse as main transcript	c.-138C>T		5_prime_UTR_variant	1/13		NM_031475.3	P1	B1AK53-1
ESPN	ENST00000636330.1 linkuse as main transcript	c.-138C>T		5_prime_UTR_variant	1/11	5

Frequencies

GnomAD3 genomes

AF:

0.0637

AC:

9646

AN:

151344

Hom.:

398

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.0934

Gnomad AMR

AF:

0.0558

Gnomad ASJ

AF:

0.0774

Gnomad EAS

AF:

0.143

Gnomad SAS

AF:

0.0643

Gnomad FIN

AF:

0.0347

Gnomad MID

AF:

0.0987

Gnomad NFE

AF:

0.0392

Gnomad OTH

AF:

0.0687

GnomAD4 exome

AF:

0.0451

AC:

33017

AN:

731772

Hom.:

994

Cov.:

AF XY:

0.0454

AC XY:

16143

AN XY:

355680

show subpopulations

Gnomad4 AFR exome

AF:

0.106

Gnomad4 AMR exome

AF:

0.0455

Gnomad4 ASJ exome

AF:

0.0864

Gnomad4 EAS exome

AF:

0.165

Gnomad4 SAS exome

AF:

0.0528

Gnomad4 FIN exome

AF:

0.0277

Gnomad4 NFE exome

AF:

0.0382

Gnomad4 OTH exome

AF:

0.0541

GnomAD4 genome

AF:

0.0638

AC:

9656

AN:

151452

Hom.:

398

Cov.:

AF XY:

0.0640

AC XY:

4733

AN XY:

73994

show subpopulations

Gnomad4 AFR

AF:

0.102

Gnomad4 AMR

AF:

0.0558

Gnomad4 ASJ

AF:

0.0774

Gnomad4 EAS

AF:

0.143

Gnomad4 SAS

AF:

0.0650

Gnomad4 FIN

AF:

0.0347

Gnomad4 NFE

AF:

0.0392

Gnomad4 OTH

AF:

0.0699

Alfa

AF:

0.0522

Hom.:

Bravo

AF:

0.0682

Asia WGS

AF:

0.0890

AC:

296

AN:

3348

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 10, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Benign

0.95

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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