1-6424818-C-T

Variant summary

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

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.11

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	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	c.-138C>T		5_prime_UTR_variant	1/13		NM_031475.3	P1
ESPN	ENST00000636330.1	c.-138C>T		5_prime_UTR_variant	1/11	5

Frequencies

GnomAD3 genomes AF: 0.0637 AC: 9646 AN: 151344 Hom.: 398 Cov.: 33

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.: 9 AF XY: 0.0454 AC XY: 16143 AN XY: 355680

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.: 33 AF XY: 0.0640 AC XY: 4733 AN XY: 73994

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.: 41

Bravo AF: 0.0682

Asia WGS AF: 0.0890 AC: 296 AN: 3348

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 10, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	16
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

Other links and lift over

dbSNP: rs182700746; hg19: chr1-6484878; COSMIC: COSV105308072; COSMIC: COSV105308072;