rs10133981

Positions:

• chr14-77269450-G-T

Variant summary

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

The NM_021257.4(NGB):​c.90-124C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0624 in 627,442 control chromosomes in the GnomAD database, including 2,962 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 0.11 (1862 hom., cov: 32)
  • Exomes 𝑓: 0.047 (1100 hom.)
• Consequence: NGB NM_021257.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.700

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NGB	NM_021257.4	c.90-124C>A		intron_variant		ENST00000298352.5	NP_067080.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NGB	ENST00000298352.5	c.90-124C>A		intron_variant		1	NM_021257.4	ENSP00000298352.4

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16678 AN: 151972 Hom.: 1861 Cov.: 32

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.0571

Gnomad AMR AF: 0.0536

Gnomad ASJ AF: 0.0478

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0599

Gnomad FIN AF: 0.0520

Gnomad MID AF: 0.0573

Gnomad NFE AF: 0.0373

Gnomad OTH AF: 0.102

GnomAD4 exome AF: 0.0472 AC: 22432 AN: 475352 Hom.: 1100 AF XY: 0.0470 AC XY: 11787 AN XY: 250876

Gnomad4 AFR exome AF: 0.293

Gnomad4 AMR exome AF: 0.0345

Gnomad4 ASJ exome AF: 0.0424

Gnomad4 EAS exome AF: 0.000172

Gnomad4 SAS exome AF: 0.0606

Gnomad4 FIN exome AF: 0.0492

Gnomad4 NFE exome AF: 0.0378

Gnomad4 OTH exome AF: 0.0568

GnomAD4 genome AF: 0.110 AC: 16690 AN: 152090 Hom.: 1862 Cov.: 32 AF XY: 0.107 AC XY: 7976 AN XY: 74348

Gnomad4 AFR AF: 0.291

Gnomad4 AMR AF: 0.0535

Gnomad4 ASJ AF: 0.0478

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0591

Gnomad4 FIN AF: 0.0520

Gnomad4 NFE AF: 0.0373

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0787 Hom.: 153

Bravo AF: 0.119

Asia WGS AF: 0.0480 AC: 167 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs10133981; hg19: chr14-77735793;