1-6424907-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.196

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 -10 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ESPN	NM_031475.3	c.-49G>A		5_prime_UTR_variant	1/13	ENST00000645284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ESPN	ENST00000645284.1	c.-49G>A		5_prime_UTR_variant	1/13		NM_031475.3	P1
ESPN	ENST00000636330.1	c.-49G>A		5_prime_UTR_variant	1/11	5

Frequencies

GnomAD3 genomes AF: 0.00178 AC: 270 AN: 151640 Hom.: 1 Cov.: 33

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.: 0 AF XY: 0.00188 AC XY: 65 AN XY: 34590

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.: 7 Cov.: 30 AF XY: 0.00122 AC XY: 754 AN XY: 618930

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.: 1 Cov.: 33 AF XY: 0.00235 AC XY: 174 AN XY: 74190

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.: 0

Bravo AF: 0.000869

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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

Other links and lift over

dbSNP: rs556298158; hg19: chr1-6484967;