NM_021257.4:c.322-105delA

Variant names:

• chr14-77266774-CT-C
• rs28909968
• NM_021257.4:c.322-105delA

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021257.4. 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
	NGB	NM_021257.4	MANE Select	c.322-105delA		intron	N/A	NP_067080.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGB	ENST00000298352.5	TSL:1 MANE Select	c.322-105delA		intron	N/A	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

African (AFR) AF: 0.140 AC: 3631 AN: 25866

American (AMR) AF: 0.344 AC: 7914 AN: 22980

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 5174 AN: 18176

East Asian (EAS) AF: 0.481 AC: 16844 AN: 34990

South Asian (SAS) AF: 0.272 AC: 16710 AN: 61360

European-Finnish (FIN) AF: 0.183 AC: 8565 AN: 46900

Middle Eastern (MID) AF: 0.234 AC: 1149 AN: 4902

European-Non Finnish (NFE) AF: 0.207 AC: 183713 AN: 886360

Other (OTH) AF: 0.233 AC: 11396 AN: 48832

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

African (AFR) AF: 0.147 AC: 6090 AN: 41502

American (AMR) AF: 0.304 AC: 4646 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1019 AN: 3472

East Asian (EAS) AF: 0.480 AC: 2476 AN: 5158

South Asian (SAS) AF: 0.278 AC: 1337 AN: 4808

European-Finnish (FIN) AF: 0.188 AC: 1997 AN: 10606

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14233 AN: 67978

Other (OTH) AF: 0.238 AC: 503 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs28909968; hg19: chr14-77733117; COSMIC: COSV107320491; COSMIC: COSV107320491;