ENST00000417816.2:c.165-4426A>G

Variant names:

• chr10-21024627-T-C
• rs661924
• ENST00000417816.2:c.165-4426A>G

Variant summary

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

The ENST00000417816.2(NEBL):​c.165-4426A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 151,968 control chromosomes in the GnomAD database, including 25,391 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 0.57 (25391 hom., cov: 31)
• Consequence: NEBL ENST00000417816.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 3 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEBL	NM_001377322.1	c.165-4426A>G		intron_variant	Intron 2 of 7		NP_001364251.1
NEBL	NM_213569.2	c.165-4426A>G		intron_variant	Intron 2 of 6		NP_998734.1
NEBL	NM_001377323.1	c.117-4426A>G		intron_variant	Intron 2 of 6		NP_001364252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEBL	ENST00000417816.2	c.165-4426A>G		intron_variant	Intron 2 of 6	1		ENSP00000393896.2
NEBL	ENST00000675114.1	n.373-4426A>G		intron_variant	Intron 4 of 8
NEBL	ENST00000675700.1	n.188-4426A>G		intron_variant	Intron 2 of 6

Frequencies

GnomAD3 genomes AF: 0.567 AC: 86115 AN: 151852 Hom.: 25371 Cov.: 31

Gnomad AFR AF: 0.397

Gnomad AMI AF: 0.691

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.579

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

GnomAD4 genome AF: 0.567 AC: 86165 AN: 151968 Hom.: 25391 Cov.: 31 AF XY: 0.573 AC XY: 42517 AN XY: 74252

African (AFR) AF: 0.397 AC: 16450 AN: 41464

American (AMR) AF: 0.657 AC: 10033 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.659 AC: 2287 AN: 3468

East Asian (EAS) AF: 0.473 AC: 2441 AN: 5156

South Asian (SAS) AF: 0.704 AC: 3383 AN: 4808

European-Finnish (FIN) AF: 0.671 AC: 7068 AN: 10540

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.625 AC: 42456 AN: 67952

Other (OTH) AF: 0.582 AC: 1225 AN: 2106

Alfa AF: 0.613 Hom.: 47454

Bravo AF: 0.552

Asia WGS AF: 0.592 AC: 2061 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.41
DANN	Benign	0.61
PhyloP100		-1.1
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: rs661924; hg19: chr10-21313556;