10-20797539-G-A

Position:

• chr10-20797539-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006393.3(NEBL):​c.2762-10231C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0792 in 152,142 control chromosomes in the GnomAD database, including 546 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.079 (546 hom., cov: 32)
• Consequence: NEBL NM_006393.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.760

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]

NEBL (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEBL	NM_006393.3	c.2762-10231C>T		intron_variant		ENST00000377122.9	NP_006384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEBL	ENST00000377122.9	c.2762-10231C>T		intron_variant		1	NM_006393.3	ENSP00000366326.4

Frequencies

GnomAD3 genomes AF: 0.0793 AC: 12049 AN: 152022 Hom.: 544 Cov.: 32

Gnomad AFR AF: 0.0998

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0911

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0546

Gnomad FIN AF: 0.0520

Gnomad MID AF: 0.0732

Gnomad NFE AF: 0.0733

Gnomad OTH AF: 0.0651

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0792 AC: 12051 AN: 152142 Hom.: 546 Cov.: 32 AF XY: 0.0787 AC XY: 5855 AN XY: 74378

Gnomad4 AFR AF: 0.0995

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.0911

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.0545

Gnomad4 FIN AF: 0.0520

Gnomad4 NFE AF: 0.0734

Gnomad4 OTH AF: 0.0640

Alfa AF: 0.0720 Hom.: 424

Bravo AF: 0.0850

Asia WGS AF: 0.0300 AC: 106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.67

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: rs10491054; hg19: chr10-21086468;