10-20785526-T-C

Variant summary

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

The NM_006393.3(NEBL):c.*221A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 578,660 control chromosomes in the GnomAD database, including 24,923 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.26 (5346 hom., cov: 32)
  • Exomes 𝑓: 0.30 (19577 hom.)
• Consequence: NEBL NM_006393.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.25

Genes affected

NEBL (HGNC:16932): (nebulette) This gene encodes a nebulin like protein that is abundantly expressed in cardiac muscle. The encoded protein binds actin and interacts with thin filaments and Z-line associated proteins in striated muscle. This protein may be involved in cardiac myofibril assembly. A shorter isoform of this protein termed LIM nebulette is expressed in non-muscle cells and may function as a component of focal adhesion complexes. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 10-20785526-T-C is Benign according to our data. Variant chr10-20785526-T-C is described in ClinVar as [Benign]. Clinvar id is 1244881.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEBL	NM_006393.3	c.*221A>G		3_prime_UTR_variant	28/28	ENST00000377122.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEBL	ENST00000377122.9	c.*221A>G		3_prime_UTR_variant	28/28	1	NM_006393.3

Frequencies

GnomAD3 genomes AF: 0.257 AC: 39016 AN: 151930 Hom.: 5342 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.278

GnomAD4 exome AF: 0.296 AC: 126144 AN: 426614 Hom.: 19577 Cov.: 4 AF XY: 0.301 AC XY: 68318 AN XY: 227124

Gnomad4 AFR exome AF: 0.179

Gnomad4 AMR exome AF: 0.240

Gnomad4 ASJ exome AF: 0.310

Gnomad4 EAS exome AF: 0.371

Gnomad4 SAS exome AF: 0.378

Gnomad4 FIN exome AF: 0.208

Gnomad4 NFE exome AF: 0.290

Gnomad4 OTH exome AF: 0.296

GnomAD4 genome AF: 0.257 AC: 39037 AN: 152046 Hom.: 5346 Cov.: 32 AF XY: 0.254 AC XY: 18892 AN XY: 74346

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.312

Gnomad4 EAS AF: 0.429

Gnomad4 SAS AF: 0.385

Gnomad4 FIN AF: 0.202

Gnomad4 NFE AF: 0.287

Gnomad4 OTH AF: 0.277

Alfa AF: 0.288 Hom.: 12252

Bravo AF: 0.256

Asia WGS AF: 0.391 AC: 1359 AN: 3478

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

Jun 15, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	11
Dann	Benign	0.74

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: rs2296613; hg19: chr10-21074455;