14-77270745-G-A

Position:

• chr14-77270745-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021257.4(NGB):​c.89+104C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 1,061,582 control chromosomes in the GnomAD database, including 127,841 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 0.41 (14744 hom., cov: 33)
  • Exomes 𝑓: 0.49 (113097 hom.)
• Consequence: NGB NM_021257.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.194

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NGB	NM_021257.4	c.89+104C>T		intron_variant		ENST00000298352.5	NP_067080.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NGB	ENST00000298352.5	c.89+104C>T		intron_variant		1	NM_021257.4	ENSP00000298352	P1

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62877 AN: 152052 Hom.: 14731 Cov.: 33

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.529

Gnomad OTH AF: 0.408

GnomAD4 exome AF: 0.492 AC: 447251 AN: 909412 Hom.: 113097 AF XY: 0.490 AC XY: 226777 AN XY: 462864

Gnomad4 AFR exome AF: 0.185

Gnomad4 AMR exome AF: 0.305

Gnomad4 ASJ exome AF: 0.464

Gnomad4 EAS exome AF: 0.453

Gnomad4 SAS exome AF: 0.391

Gnomad4 FIN exome AF: 0.580

Gnomad4 NFE exome AF: 0.521

Gnomad4 OTH exome AF: 0.466

GnomAD4 genome AF: 0.413 AC: 62906 AN: 152170 Hom.: 14744 Cov.: 33 AF XY: 0.416 AC XY: 30976 AN XY: 74396

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.346

Gnomad4 ASJ AF: 0.455

Gnomad4 EAS AF: 0.446

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.587

Gnomad4 NFE AF: 0.529

Gnomad4 OTH AF: 0.415

Alfa AF: 0.488 Hom.: 2429

Bravo AF: 0.384

Asia WGS AF: 0.436 AC: 1513 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.3
DANN	Benign	0.97

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

Publications

LitVar

Other links and lift over

dbSNP: rs4903565; hg19: chr14-77737088; COSMIC: COSV53612154; COSMIC: COSV53612154;