Genetic Variant NGB:c.90-124C>A (chr14-77269450-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.700

Publications

6 publications found

Variant links:

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]

NGB links:

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ACMG classification

Classification was made for transcript

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.

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.90-124C>A		intron	N/A	NP_067080.1	Q9NPG2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NGB	ENST00000298352.5	TSL:1 MANE Select	c.90-124C>A		intron	N/A	ENSP00000298352.4	Q9NPG2

Frequencies

GnomAD3 genomes

AF:

0.110

AC:

16678

AN:

151972

Hom.:

1861

Cov.:

show subpopulations

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

show subpopulations

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:

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

988

1976

2965

3953

4941

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

240

360

480

600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.110

AC:

16690

AN:

152090

Hom.:

1862

Cov.:

AF XY:

0.107

AC XY:

7976

AN XY:

74348

show subpopulations

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:

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:

AN:

292

European-Non Finnish (NFE)

AF:

0.0373

AC:

2534

AN:

67978

Other (OTH)

AF:

0.101

AC:

213

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

664

1328

1993

2657

3321

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

162

324

486

648

810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.8

(source)

DANN

Benign

0.66

PhyloP100

-0.70

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over