rs10828151

Variant names:

• chr10-20922826-A-C
• rs10828151
• ENST00000417816.2:c.357+38846T>G

Variant summary

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

The NM_001377322.1(NEBL):​c.357+38846T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0626 in 152,186 control chromosomes in the GnomAD database, including 467 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 0.063 (467 hom., cov: 32)
• Consequence: NEBL NM_001377322.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.437
• Publications: 5 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

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 (EAS) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377322.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEBL	NM_001377322.1		c.357+38846T>G		intron	N/A	NP_001364251.1
	NEBL	NM_213569.2		c.357+38846T>G		intron	N/A	NP_998734.1	Q59FZ8
	NEBL	NM_001377323.1		c.309+38846T>G		intron	N/A	NP_001364252.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEBL	ENST00000417816.2	TSL:1	c.357+38846T>G		intron	N/A	ENSP00000393896.2	O76041-2
	NEBL	ENST00000674540.1		n.296-23376T>G		intron	N/A
	NEBL	ENST00000675114.1		n.565+38846T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0626 AC: 9519 AN: 152068 Hom.: 464 Cov.: 32

Gnomad AFR AF: 0.0203

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.0687

Gnomad FIN AF: 0.0223

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0636

Gnomad OTH AF: 0.0908

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

GnomAD4 genome AF: 0.0626 AC: 9528 AN: 152186 Hom.: 467 Cov.: 32 AF XY: 0.0629 AC XY: 4681 AN XY: 74400

African (AFR) AF: 0.0203 AC: 844 AN: 41542

American (AMR) AF: 0.137 AC: 2093 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 601 AN: 3472

East Asian (EAS) AF: 0.155 AC: 801 AN: 5158

South Asian (SAS) AF: 0.0684 AC: 329 AN: 4812

European-Finnish (FIN) AF: 0.0223 AC: 236 AN: 10602

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.0636 AC: 4328 AN: 68002

Other (OTH) AF: 0.0903 AC: 190 AN: 2104

Alfa AF: 0.0662 Hom.: 971

Bravo AF: 0.0732

Asia WGS AF: 0.111 AC: 387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.5
DANN	Benign	0.66
PhyloP100		0.44
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: rs10828151; hg19: chr10-21211755;