chr10-20851326-A-C

Variant names:

• chr10-20851326-A-C
• rs703088
• NM_006393.3:c.1009-824T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006393.3(NEBL):​c.1009-824T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.923 in 152,004 control chromosomes in the GnomAD database, including 64,845 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 0.92 (64845 hom., cov: 32)
• Consequence: NEBL NM_006393.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.62
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• dilated cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

LOC102725112 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006393.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEBL	NM_006393.3	MANE Select	c.1009-824T>G		intron	N/A	NP_006384.1
	NEBL	NM_001377322.1		c.358-38386T>G		intron	N/A	NP_001364251.1
	NEBL	NM_213569.2		c.358-38386T>G		intron	N/A	NP_998734.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEBL	ENST00000377122.9	TSL:1 MANE Select	c.1009-824T>G		intron	N/A	ENSP00000366326.4
	NEBL	ENST00000417816.2	TSL:1	c.358-38386T>G		intron	N/A	ENSP00000393896.2
	NEBL	ENST00000675114.1		n.566-38386T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.923 AC: 140208 AN: 151888 Hom.: 64796 Cov.: 32

Gnomad AFR AF: 0.908

Gnomad AMI AF: 0.969

Gnomad AMR AF: 0.867

Gnomad ASJ AF: 0.936

Gnomad EAS AF: 0.907

Gnomad SAS AF: 0.935

Gnomad FIN AF: 0.929

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.943

Gnomad OTH AF: 0.928

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

GnomAD4 genome AF: 0.923 AC: 140314 AN: 152004 Hom.: 64845 Cov.: 32 AF XY: 0.921 AC XY: 68477 AN XY: 74318

African (AFR) AF: 0.909 AC: 37684 AN: 41476

American (AMR) AF: 0.866 AC: 13228 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.936 AC: 3248 AN: 3470

East Asian (EAS) AF: 0.907 AC: 4682 AN: 5162

South Asian (SAS) AF: 0.936 AC: 4509 AN: 4818

European-Finnish (FIN) AF: 0.929 AC: 9755 AN: 10506

Middle Eastern (MID) AF: 0.952 AC: 280 AN: 294

European-Non Finnish (NFE) AF: 0.943 AC: 64083 AN: 67982

Other (OTH) AF: 0.929 AC: 1961 AN: 2112

Alfa AF: 0.934 Hom.: 117139

Bravo AF: 0.917

Asia WGS AF: 0.930 AC: 3226 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.87
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs703088; hg19: chr10-21140255;