rs3847375

Positions:

• chr10-21278636-C-A
• chr10-21278636-C-T

Variant summary

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

The NM_001377326.1(NEBL):​c.-40+14194G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 152,040 control chromosomes in the GnomAD database, including 11,014 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 0.30 (11014 hom., cov: 32)
• Consequence: NEBL NM_001377326.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.518

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEBL	NM_001377326.1	c.-40+14194G>T		intron_variant			NP_001364255.1
NEBL	NM_001377327.1	c.-206+14194G>T		intron_variant			NP_001364256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEBL	ENST00000675702.1	n.182+14194G>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45091 AN: 151922 Hom.: 10979 Cov.: 32

Gnomad AFR AF: 0.676

Gnomad AMI AF: 0.244

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.0150

Gnomad SAS AF: 0.0993

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.297 AC: 45175 AN: 152040 Hom.: 11014 Cov.: 32 AF XY: 0.288 AC XY: 21408 AN XY: 74320

Gnomad4 AFR AF: 0.676

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.0147

Gnomad4 SAS AF: 0.0989

Gnomad4 FIN AF: 0.132

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.260

Alfa AF: 0.176 Hom.: 2431

Bravo AF: 0.322

Asia WGS AF: 0.114 AC: 395 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.0
DANN	Benign	0.51

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3847375; hg19: chr10-21567565;