14-77269450-G-T

Variant names:

• chr14-77269450-G-T
• rs10133981
• NM_021257.4:c.90-124C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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 -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 rank	MANE	Protein	UniProt
NGB	NM_021257.4	c.90-124C>A		intron_variant	Intron 1 of 3	ENST00000298352.5	NP_067080.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NGB	ENST00000298352.5	c.90-124C>A		intron_variant	Intron 1 of 3	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

African (AFR) AF: 0.293 AC: 3941 AN: 13448

American (AMR) AF: 0.0345 AC: 896 AN: 25996

Ashkenazi Jewish (ASJ) AF: 0.0424 AC: 597 AN: 14092

East Asian (EAS) AF: 0.000172 AC: 5 AN: 29038

South Asian (SAS) AF: 0.0606 AC: 3091 AN: 51020

European-Finnish (FIN) AF: 0.0492 AC: 1987 AN: 40378

Middle Eastern (MID) AF: 0.0599 AC: 120 AN: 2004

European-Non Finnish (NFE) AF: 0.0378 AC: 10340 AN: 273766

Other (OTH) AF: 0.0568 AC: 1455 AN: 25610

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

African (AFR) AF: 0.291 AC: 12051 AN: 41456

American (AMR) AF: 0.0535 AC: 818 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0478 AC: 166 AN: 3470

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5166

South Asian (SAS) AF: 0.0591 AC: 285 AN: 4820

European-Finnish (FIN) AF: 0.0520 AC: 552 AN: 10608

Middle Eastern (MID) AF: 0.0582 AC: 17 AN: 292

European-Non Finnish (NFE) AF: 0.0373 AC: 2534 AN: 67978

Other (OTH) AF: 0.101 AC: 213 AN: 2114

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
PhyloP100		-0.70
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10133981; hg19: chr14-77735793;