14-77268237-T-C

Position:

• chr14-77268237-T-C

Variant summary

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

The NM_021257.4(NGB):​c.321+229A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 151,910 control chromosomes in the GnomAD database, including 3,993 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 0.22 (3993 hom., cov: 32)
• Consequence: NGB NM_021257.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.938

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NGB	NM_021257.4	c.321+229A>G		intron_variant		ENST00000298352.5	NP_067080.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NGB	ENST00000298352.5	c.321+229A>G		intron_variant		1	NM_021257.4	ENSP00000298352	P1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32807 AN: 151794 Hom.: 3988 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.290

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.240

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.216 AC: 32823 AN: 151910 Hom.: 3993 Cov.: 32 AF XY: 0.220 AC XY: 16324 AN XY: 74242

Gnomad4 AFR AF: 0.145

Gnomad4 AMR AF: 0.306

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.487

Gnomad4 SAS AF: 0.281

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.239

Alfa AF: 0.221 Hom.: 5069

Bravo AF: 0.225

Asia WGS AF: 0.348 AC: 1211 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.68

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: rs3783988; hg19: chr14-77734580;