10-21173940-C-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• 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 -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 VariationId 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.

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.-107G>T		5_prime_UTR	Exon 1 of 8	NP_001364251.1
	NEBL	NM_213569.2		c.-107G>T		5_prime_UTR	Exon 1 of 7	NP_998734.1	Q59FZ8
	NEBL	NM_001377324.1		c.-265G>T		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.-107G>T		5_prime_UTR	Exon 1 of 7	ENSP00000393896.2	O76041-2
	NEBL-AS1	ENST00000737816.1		n.30C>A		non_coding_transcript_exon	Exon 1 of 2
	NEBL	ENST00000675700.1		n.92+900G>T		intron	N/A

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

African (AFR) AF: 0.106 AC: 2538 AN: 23964

American (AMR) AF: 0.00931 AC: 119 AN: 12784

Ashkenazi Jewish (ASJ) AF: 0.000243 AC: 4 AN: 16458

East Asian (EAS) AF: 0.00 AC: 0 AN: 28712

South Asian (SAS) AF: 0.000157 AC: 9 AN: 57386

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30054

Middle Eastern (MID) AF: 0.00606 AC: 23 AN: 3794

European-Non Finnish (NFE) AF: 0.000174 AC: 177 AN: 1016574

Other (OTH) AF: 0.00691 AC: 351 AN: 50772

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

African (AFR) AF: 0.0951 AC: 3937 AN: 41400

American (AMR) AF: 0.0106 AC: 161 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5076

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10442

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

European-Non Finnish (NFE) AF: 0.000531 AC: 36 AN: 67802

Other (OTH) AF: 0.0138 AC: 29 AN: 2108

Alfa AF: 0.0209 Hom.: 9

Bravo AF: 0.0315

Asia WGS AF: 0.00408 AC: 15 AN: 3444

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	10
DANN	Benign	0.92
PhyloP100		-0.60
PromoterAI		0.011	Neutral
Mutation Taster		=299/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs113394390; hg19: chr10-21462869;