rs10828151

Positions:

• chr10-20922826-A-C

Variant summary

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

The ENST00000417816.2(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 ENST00000417816.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.437

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEBL	NM_001173484.2	c.357+38846T>G		intron_variant			NP_001166955.1
NEBL	NM_001377322.1	c.357+38846T>G		intron_variant			NP_001364251.1
NEBL	NM_001377323.1	c.309+38846T>G		intron_variant			NP_001364252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEBL	ENST00000417816.2	c.357+38846T>G		intron_variant		1		ENSP00000393896	P1
NEBL	ENST00000674540.1	n.296-23376T>G		intron_variant, non_coding_transcript_variant
NEBL	ENST00000675114.1	n.565+38846T>G		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.0203

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.0684

Gnomad4 FIN AF: 0.0223

Gnomad4 NFE AF: 0.0636

Gnomad4 OTH AF: 0.0903

Alfa AF: 0.0659 Hom.: 218

Bravo AF: 0.0732

Asia WGS AF: 0.111 AC: 387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.5
DANN	Benign	0.66

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: rs10828151; hg19: chr10-21211755;