rs10491054

Variant names:

• chr10-20797539-G-A
• rs10491054
• NM_006393.3:c.2762-10231C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-20797539-G-A
• chr10-20797539-G-T

Variant summary

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

The NM_006393.3(NEBL):​c.2762-10231C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0792 in 152,142 control chromosomes in the GnomAD database, including 546 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 0.079 (546 hom., cov: 32)
• Consequence: NEBL NM_006393.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.760
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.1 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEBL	NM_006393.3	MANE Select	c.2762-10231C>T		intron	N/A	NP_006384.1
	NEBL	NM_001377322.1		c.623-10231C>T		intron	N/A	NP_001364251.1
	NEBL	NM_213569.2		c.530-10231C>T		intron	N/A	NP_998734.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEBL	ENST00000377122.9	TSL:1 MANE Select	c.2762-10231C>T		intron	N/A	ENSP00000366326.4
	NEBL	ENST00000417816.2	TSL:1	c.530-10231C>T		intron	N/A	ENSP00000393896.2
	NEBL	ENST00000863069.1		c.2771-10231C>T		intron	N/A	ENSP00000533128.1

Frequencies

GnomAD3 genomes AF: 0.0793 AC: 12049 AN: 152022 Hom.: 544 Cov.: 32

Gnomad AFR AF: 0.0998

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0911

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.0546

Gnomad FIN AF: 0.0520

Gnomad MID AF: 0.0732

Gnomad NFE AF: 0.0733

Gnomad OTH AF: 0.0651

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

GnomAD4 genome AF: 0.0792 AC: 12051 AN: 152142 Hom.: 546 Cov.: 32 AF XY: 0.0787 AC XY: 5855 AN XY: 74378

African (AFR) AF: 0.0995 AC: 4131 AN: 41516

American (AMR) AF: 0.105 AC: 1600 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0911 AC: 316 AN: 3468

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5170

South Asian (SAS) AF: 0.0545 AC: 262 AN: 4810

European-Finnish (FIN) AF: 0.0520 AC: 551 AN: 10588

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0734 AC: 4988 AN: 68002

Other (OTH) AF: 0.0640 AC: 135 AN: 2110

Alfa AF: 0.0748 Hom.: 595

Bravo AF: 0.0850

Asia WGS AF: 0.0300 AC: 106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.67
PhyloP100		0.76
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: rs10491054; hg19: chr10-21086468;