14-77266774-CTT-C

Variant names:

• chr14-77266774-CTT-C
• rs28909968
• NM_021257.4:c.322-106_322-105delAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_021257.4(NGB):​c.322-106_322-105delAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000868 in 1,151,986 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 8.7e-7 (0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGB	NM_021257.4	MANE Select	c.322-106_322-105delAA		intron	N/A	NP_067080.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGB	ENST00000298352.5	TSL:1 MANE Select	c.322-106_322-105delAA		intron	N/A	ENSP00000298352.4

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 8.68e-7 AC: 1 AN: 1151986 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 568276

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 25886

American (AMR) AF: 0.00 AC: 0 AN: 23024

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18204

East Asian (EAS) AF: 0.00 AC: 0 AN: 35030

South Asian (SAS) AF: 0.0000163 AC: 1 AN: 61464

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46928

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4906

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 887636

Other (OTH) AF: 0.00 AC: 0 AN: 48908

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;