chr10-21173967-GGC-G

Variant names:

• chr10-21173967-GGC-G
• rs778464499
• ENST00000417816.2:c.-136_-135delGC

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001377322.1(NEBL):​c.-136_-135delGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 1,357,608 control chromosomes in the GnomAD database, including 108 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0082 (10 hom., cov: 32)
  • Exomes 𝑓: 0.012 (98 hom.)
• Consequence: NEBL NM_001377322.1 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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-AS1 (HGNC:44899): (NEBL antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 10-21173967-GGC-G is Benign according to our data. Variant chr10-21173967-GGC-G is described in ClinVar as [Likely_benign]. Clinvar id is 1315972.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEBL	NM_001377322.1	c.-136_-135delGC		5_prime_UTR_variant	Exon 1 of 8		NP_001364251.1
NEBL	NM_213569.2	c.-136_-135delGC		5_prime_UTR_variant	Exon 1 of 7		NP_998734.1
NEBL	NM_001377324.1	c.-294_-293delGC		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.-136_-135delGC		5_prime_UTR_variant	Exon 1 of 7	1		ENSP00000393896.2
NEBL	ENST00000675700.1	n.92+871_92+872delGC		intron_variant	Intron 1 of 6
NEBL	ENST00000675702.1	n.349-1492_349-1491delGC		intron_variant	Intron 3 of 8

Frequencies

GnomAD3 genomes AF: 0.00816 AC: 1237 AN: 151512 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.00206

Gnomad AMI AF: 0.0728

Gnomad AMR AF: 0.00651

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00786

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0130

Gnomad OTH AF: 0.00240

GnomAD4 exome AF: 0.0121 AC: 14572 AN: 1205988 Hom.: 98 AF XY: 0.0118 AC XY: 6948 AN XY: 588328

Gnomad4 AFR exome AF: 0.00141

Gnomad4 AMR exome AF: 0.00341

Gnomad4 ASJ exome AF: 0.00578

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000388

Gnomad4 FIN exome AF: 0.00817

Gnomad4 NFE exome AF: 0.0138

Gnomad4 OTH exome AF: 0.00899

GnomAD4 genome AF: 0.00817 AC: 1238 AN: 151620 Hom.: 10 Cov.: 32 AF XY: 0.00775 AC XY: 574 AN XY: 74096

Gnomad4 AFR AF: 0.00205

Gnomad4 AMR AF: 0.00650

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00786

Gnomad4 NFE AF: 0.0130

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00983 Hom.: 1

Bravo AF: 0.00754

Asia WGS AF: 0.000293 AC: 1 AN: 3422

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 16, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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: rs778464499; hg19: chr10-21462896;