rs703088

Positions:

• chr10-20851326-A-C
• chr10-20851326-A-G
• chr10-20851326-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

LOC102725112 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEBL	NM_006393.3	c.1009-824T>G		intron_variant		ENST00000377122.9
LOC102725112	XR_007062082.1	n.223+2800A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEBL	ENST00000377122.9	c.1009-824T>G		intron_variant		1	NM_006393.3

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

Gnomad4 AFR AF: 0.909

Gnomad4 AMR AF: 0.866

Gnomad4 ASJ AF: 0.936

Gnomad4 EAS AF: 0.907

Gnomad4 SAS AF: 0.936

Gnomad4 FIN AF: 0.929

Gnomad4 NFE AF: 0.943

Gnomad4 OTH AF: 0.929

Alfa AF: 0.933 Hom.: 38441

Bravo AF: 0.917

Asia WGS AF: 0.930 AC: 3226 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	11
DANN	Benign	0.87

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: rs703088; hg19: chr10-21140255;