rs545718319

Variant names:

• chr10-21174056-TCGGCTC-T
• rs545718319
• ENST00000417816.2:c.-229_-224delGAGCCG

Your query was ambiguous. Multiple possible variants found:

• chr10-21174056-TCGGCTC-T
• chr10-21174056-TCGGCTC-TCGGCTCCGGCTC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.40
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1162 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377322.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEBL	NM_001377322.1		c.-229_-224delGAGCCG		5_prime_UTR	Exon 1 of 8	NP_001364251.1
	NEBL	NM_213569.2		c.-229_-224delGAGCCG		5_prime_UTR	Exon 1 of 7	NP_998734.1	Q59FZ8
	NEBL	NM_001377324.1		c.-387_-382delGAGCCG		5_prime_UTR	Exon 1 of 7	NP_001364253.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEBL	ENST00000417816.2	TSL:1	c.-229_-224delGAGCCG		5_prime_UTR	Exon 1 of 7	ENSP00000393896.2	O76041-2
	NEBL-AS1	ENST00000439097.2	TSL:2	n.61_66delGCTCCG		non_coding_transcript_exon	Exon 1 of 2
	NEBL	ENST00000675700.1		n.92+778_92+783delGAGCCG		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00766 AC: 1161 AN: 151536 Hom.: 14 Cov.: 32

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.: 6 AF XY: 0.000662 AC XY: 300 AN XY: 453424

African (AFR) AF: 0.0272 AC: 518 AN: 19016

American (AMR) AF: 0.00352 AC: 16 AN: 4540

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9234

East Asian (EAS) AF: 0.00 AC: 0 AN: 13552

South Asian (SAS) AF: 0.00 AC: 0 AN: 18354

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12448

Middle Eastern (MID) AF: 0.00177 AC: 4 AN: 2262

European-Non Finnish (NFE) AF: 0.000113 AC: 96 AN: 847644

Other (OTH) AF: 0.00175 AC: 62 AN: 35434

GnomAD4 genome AF: 0.00766 AC: 1162 AN: 151644 Hom.: 14 Cov.: 32 AF XY: 0.00735 AC XY: 545 AN XY: 74102

African (AFR) AF: 0.0257 AC: 1063 AN: 41394

American (AMR) AF: 0.00465 AC: 71 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5090

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10482

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000295 AC: 20 AN: 67846

Other (OTH) AF: 0.00382 AC: 8 AN: 2096

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00927

Asia WGS AF: 0.000585 AC: 2 AN: 3434

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4
Mutation Taster		=300/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs545718319; hg19: chr10-21462985;