Genetic Variant NEBL:c.-229_-224delGAGCCG (chr10-21174056-TCGGCTC-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_001377322.1(NEBL):c.-229_-224delGAGCCG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00167 in 1,114,128 control chromosomes in the GnomAD database, including 20 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0077 ( 14 hom., cov: 32)

Exomes 𝑓: 0.00072 ( 6 hom. )

Consequence

NEBL
NM_001377322.1 5_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.40

Variant links:

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 links:

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

NEBL-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 10-21174056-TCGGCTC-T is Benign according to our data. Variant chr10-21174056-TCGGCTC-T is described in ClinVar as [Likely_benign]. Clinvar id is 1318446.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00766 (1162/151644) while in subpopulation AFR AF= 0.0257 (1063/41394). AF 95% confidence interval is 0.0244. There are 14 homozygotes in gnomad4. There are 545 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
NEBL	NM_001377322.1 link	c.-229_-224delGAGCCG	5_prime_UTR_variant	Exon 1 of 8	NP_001364251.1
NEBL	NM_213569.2 link	c.-229_-224delGAGCCG	5_prime_UTR_variant	Exon 1 of 7	NP_998734.1	O76041-2Q59FZ8
NEBL	NM_001377324.1 link	c.-387_-382delGAGCCG	5_prime_UTR_variant	Exon 1 of 7	NP_001364253.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
NEBL	ENST00000417816.2 link	c.-229_-224delGAGCCG	5_prime_UTR_variant	Exon 1 of 7	1	ENSP00000393896.2	O76041-2
NEBL-AS1	ENST00000439097.1 link	n.58_63delGCTCCG	non_coding_transcript_exon_variant	Exon 1 of 2	2
NEBL	ENST00000675700.1 link	n.92+778_92+783delGAGCCG	intron_variant	Intron 1 of 6

Frequencies

GnomAD3 genomes

AF:

0.00766

AC:

1161

AN:

151536

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0257

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00466

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000295

Gnomad OTH

AF:

0.00386

GnomAD4 exome

AF:

0.000723

AC:

696

AN:

962484

Hom.:

AF XY:

0.000662

AC XY:

300

AN XY:

453424

show subpopulations

Gnomad4 AFR exome

AF:

0.0272

Gnomad4 AMR exome

AF:

0.00352

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000113

Gnomad4 OTH exome

AF:

0.00175

GnomAD4 genome

AF:

0.00766

AC:

1162

AN:

151644

Hom.:

Cov.:

AF XY:

0.00735

AC XY:

545

AN XY:

74102

show subpopulations

Gnomad4 AFR

AF:

0.0257

Gnomad4 AMR

AF:

0.00465

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000295

Gnomad4 OTH

AF:

0.00382

Bravo

AF:

0.00927

Asia WGS

AF:

0.000585

AC:

AN:

3434

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 07, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over