14-77266774-CTT-CT

Position:

• chr14-77266774-CTT-CT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_021257.4(NGB):​c.322-105delA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 1,302,502 control chromosomes in the GnomAD database, including 34,935 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (3936 hom., cov: 28)
  • Exomes 𝑓: 0.22 (30999 hom.)
• Consequence: NGB NM_021257.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118

Genes affected

NGB (HGNC:14077): (neuroglobin) This gene encodes an oxygen-binding protein that is distantly related to members of the globin gene family. It is highly conserved among other vertebrates. It is expressed in the central and peripheral nervous system where it may be involved in increasing oxygen availability and providing protection under hypoxic/ischemic conditions. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NGB	NM_021257.4	c.322-105delA		intron_variant		ENST00000298352.5	NP_067080.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NGB	ENST00000298352.5	c.322-105delA		intron_variant		1	NM_021257.4	ENSP00000298352.4

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32599 AN: 152014 Hom.: 3931 Cov.: 28

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.481

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.239

GnomAD4 exome AF: 0.222 AC: 255096 AN: 1150366 Hom.: 30999 AF XY: 0.223 AC XY: 126326 AN XY: 567428

Gnomad4 AFR exome AF: 0.140

Gnomad4 AMR exome AF: 0.344

Gnomad4 ASJ exome AF: 0.285

Gnomad4 EAS exome AF: 0.481

Gnomad4 SAS exome AF: 0.272

Gnomad4 FIN exome AF: 0.183

Gnomad4 NFE exome AF: 0.207

Gnomad4 OTH exome AF: 0.233

GnomAD4 genome AF: 0.214 AC: 32619 AN: 152136 Hom.: 3936 Cov.: 28 AF XY: 0.218 AC XY: 16206 AN XY: 74400

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.304

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.480

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.238

Alfa AF: 0.0808 Hom.: 110

Bravo AF: 0.224

Asia WGS AF: 0.337 AC: 1175 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs28909968; hg19: chr14-77733117;