10-21173940-C-A

Variant names:

• chr10-21173940-C-A
• rs113394390
• ENST00000417816.2:c.-107G>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001377322.1(NEBL):​c.-107G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00531 in 1,392,060 control chromosomes in the GnomAD database, including 382 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.027 (205 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (177 hom.)
• Consequence: NEBL NM_001377322.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.604

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-AS1 (HGNC:44899): (NEBL antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 10-21173940-C-A is Benign according to our data. Variant chr10-21173940-C-A is described in ClinVar as [Benign]. Clinvar id is 1247301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEBL	NM_001377322.1	c.-107G>T		5_prime_UTR_variant	Exon 1 of 8		NP_001364251.1
NEBL	NM_213569.2	c.-107G>T		5_prime_UTR_variant	Exon 1 of 7		NP_998734.1
NEBL	NM_001377324.1	c.-265G>T		5_prime_UTR_variant	Exon 1 of 7		NP_001364253.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEBL	ENST00000417816.2	c.-107G>T		5_prime_UTR_variant	Exon 1 of 7	1		ENSP00000393896.2
NEBL	ENST00000675700.1	n.92+900G>T		intron_variant	Intron 1 of 6
NEBL	ENST00000675702.1	n.349-1463G>T		intron_variant	Intron 3 of 8

Frequencies

GnomAD3 genomes AF: 0.0275 AC: 4160 AN: 151454 Hom.: 205 Cov.: 32

Gnomad AFR AF: 0.0952

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0106

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000531

Gnomad OTH AF: 0.0139

GnomAD4 exome AF: 0.00260 AC: 3221 AN: 1240498 Hom.: 177 Cov.: 31 AF XY: 0.00226 AC XY: 1373 AN XY: 606280

Gnomad4 AFR exome AF: 0.106

Gnomad4 AMR exome AF: 0.00931

Gnomad4 ASJ exome AF: 0.000243

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000157

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000174

Gnomad4 OTH exome AF: 0.00691

GnomAD4 genome AF: 0.0275 AC: 4165 AN: 151562 Hom.: 205 Cov.: 32 AF XY: 0.0261 AC XY: 1935 AN XY: 74104

Gnomad4 AFR AF: 0.0951

Gnomad4 AMR AF: 0.0106

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000531

Gnomad4 OTH AF: 0.0138

Alfa AF: 0.0209 Hom.: 9

Bravo AF: 0.0315

Asia WGS AF: 0.00408 AC: 15 AN: 3444

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 07, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	10
DANN	Benign	0.92

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: rs113394390; hg19: chr10-21462869;