rs11012461

Positions:

• chr10-20986398-G-A

Variant summary

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

The ENST00000417816.2(NEBL):​c.250-24619C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,010 control chromosomes in the GnomAD database, including 2,406 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 0.13 (2406 hom., cov: 32)
• Consequence: NEBL ENST00000417816.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07

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 = 0.368 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEBL	NM_001173484.2	c.250-24619C>T		intron_variant			NP_001166955.1
NEBL	NM_001377322.1	c.250-24619C>T		intron_variant			NP_001364251.1
NEBL	NM_001377323.1	c.202-24619C>T		intron_variant			NP_001364252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEBL	ENST00000417816.2	c.250-24619C>T		intron_variant		1		ENSP00000393896	P1
NEBL	ENST00000674777.1	n.63+16236C>T		intron_variant, non_coding_transcript_variant
NEBL	ENST00000675114.1	n.458-24619C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19477 AN: 151892 Hom.: 2395 Cov.: 32

Gnomad AFR AF: 0.298

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0534

Gnomad ASJ AF: 0.0505

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.0767

Gnomad FIN AF: 0.0994

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0367

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.128 AC: 19526 AN: 152010 Hom.: 2406 Cov.: 32 AF XY: 0.132 AC XY: 9786 AN XY: 74332

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.0533

Gnomad4 ASJ AF: 0.0505

Gnomad4 EAS AF: 0.382

Gnomad4 SAS AF: 0.0769

Gnomad4 FIN AF: 0.0994

Gnomad4 NFE AF: 0.0367

Gnomad4 OTH AF: 0.110

Alfa AF: 0.0380 Hom.: 284

Bravo AF: 0.135

Asia WGS AF: 0.213 AC: 739 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	9.4
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: rs11012461; hg19: chr10-21275327;