ENST00000417816.2:c.165-9762T>C

Variant names:

• chr10-21029963-A-G
• rs67179
• ENST00000417816.2:c.165-9762T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000417816.2(NEBL):​c.165-9762T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 541,278 control chromosomes in the GnomAD database, including 107,038 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.59 (26696 hom., cov: 31)
  • Exomes 𝑓: 0.64 (80342 hom.)
• Consequence: NEBL ENST00000417816.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0630
• Publications: 2 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]

EIF4BP2 (HGNC:37935): (eukaryotic translation initiation factor 4B pseudogene 2)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000417816.2. 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.165-9762T>C		intron	N/A	NP_001364251.1
	NEBL	NM_213569.2		c.165-9762T>C		intron	N/A	NP_998734.1	Q59FZ8
	NEBL	NM_001377323.1		c.117-9762T>C		intron	N/A	NP_001364252.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEBL	ENST00000417816.2	TSL:1	c.165-9762T>C		intron	N/A	ENSP00000393896.2	O76041-2
	EIF4BP2	ENST00000416702.1	TSL:6	n.965A>G		non_coding_transcript_exon	Exon 1 of 1
	NEBL	ENST00000675114.1		n.373-9762T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.591 AC: 89702 AN: 151692 Hom.: 26666 Cov.: 31

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.529

Gnomad EAS AF: 0.725

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.594

GnomAD4 exome AF: 0.640 AC: 249387 AN: 389470 Hom.: 80342 Cov.: 0 AF XY: 0.641 AC XY: 135531 AN XY: 211564

African (AFR) AF: 0.511 AC: 5681 AN: 11114

American (AMR) AF: 0.681 AC: 15620 AN: 22924

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 5340 AN: 9734

East Asian (EAS) AF: 0.744 AC: 15235 AN: 20478

South Asian (SAS) AF: 0.668 AC: 33049 AN: 49482

European-Finnish (FIN) AF: 0.670 AC: 24552 AN: 36636

Middle Eastern (MID) AF: 0.578 AC: 775 AN: 1340

European-Non Finnish (NFE) AF: 0.627 AC: 136467 AN: 217746

Other (OTH) AF: 0.633 AC: 12668 AN: 20016

GnomAD4 genome AF: 0.591 AC: 89785 AN: 151808 Hom.: 26696 Cov.: 31 AF XY: 0.594 AC XY: 44066 AN XY: 74182

African (AFR) AF: 0.511 AC: 21107 AN: 41280

American (AMR) AF: 0.624 AC: 9532 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.529 AC: 1834 AN: 3468

East Asian (EAS) AF: 0.725 AC: 3739 AN: 5154

South Asian (SAS) AF: 0.668 AC: 3215 AN: 4816

European-Finnish (FIN) AF: 0.648 AC: 6839 AN: 10550

Middle Eastern (MID) AF: 0.531 AC: 155 AN: 292

European-Non Finnish (NFE) AF: 0.613 AC: 41654 AN: 67952

Other (OTH) AF: 0.594 AC: 1254 AN: 2112

Alfa AF: 0.486 Hom.: 1510

Bravo AF: 0.585

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.9
DANN	Benign	0.46
PhyloP100		0.063
Mutation Taster		=100/0	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs67179;

hg19: chr10-21318892;

COSMIC: COSV65841033;