10-21167926-A-T

Position:

• chr10-21167926-A-T

Variant summary

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

The NM_001377322.1(NEBL):​c.164+4457T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 152,176 control chromosomes in the GnomAD database, including 1,799 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 0.15 (1799 hom., cov: 32)
• Consequence: NEBL NM_001377322.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEBL	NM_001377322.1	c.164+4457T>A		intron_variant			NP_001364251.1
NEBL	NM_213569.2	c.164+4457T>A		intron_variant			NP_998734.1
NEBL	NM_001377323.1	c.116+4457T>A		intron_variant			NP_001364252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEBL	ENST00000417816.2	c.164+4457T>A		intron_variant		1		ENSP00000393896.2
NEBL	ENST00000675700.1	n.187+4457T>A		intron_variant
NEBL	ENST00000675702.1	n.443+4457T>A		intron_variant
NEBL	ENST00000675747.1	n.224+4457T>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23142 AN: 152058 Hom.: 1793 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.153

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.152 AC: 23161 AN: 152176 Hom.: 1799 Cov.: 32 AF XY: 0.151 AC XY: 11266 AN XY: 74390

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.164

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.126

Alfa AF: 0.0764 Hom.: 81

Bravo AF: 0.152

Asia WGS AF: 0.214 AC: 742 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	7.9
DANN	Benign	0.71

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: rs1979487; hg19: chr10-21456855;